Tag Archives: stem cells

Cooking up a lung one way or the other

I have two stories about lungs and they are entirely different with the older one being a bioengineering story from the US and the more recent one being an artificial tissue story from the University of Toronto and the University of Ottawa (both in Canada).

Lab grown lungs

The Canadian Broadcasting Corporation’s Quirks and Quarks radio programme posted a December 29, 2018 news item (with embedded radio files) about bioengineered lunjgs,

There are two major components to building an organ: the structure and the right cells on that structure. A team led by Dr. Joan Nichols, a Professor of Internal Medicine, Microbiology and Immunology at the University of Texas Medical Branch in Galveston, were able to tackle both parts of the problem

In their experiment they used a donor organ for the structure. They took a lung from an unrelated pig, and stripped it of its cells, leaving a scaffold of collagen, a tough, flexible protein.  This provided a pre-made appropriate structure, though in future they think it may be possible to use 3-D printing technology to get the same result.

They then added cultured cells from the animal who would be receiving the transplant – so the lung was made of the animal’s own cells. Cultured lung and blood vessel cells were placed on the scaffold and it was  placed in a tank for 30 days with a cocktail of nutrients to help the cells stick to the scaffold and proliferate. The result was a kind of baby lung.

They then transplanted the bio-engineered, though immature, lung into the recipient animal where they hoped it would continue to develop and mature – growing to become a healthy, functioning organ.

The recipients of the bio-engineered lungs were four pigs adult pigs, which appeared to tolerate the transplants well. In order to study the development of the bio-engineered lungs, they euthanized the animals at different times: 10 hours, two weeks, one month and two months after transplantation.

They found that as early as two weeks, the bio-engineered lung had integrated into the recipient animals’ body, building a strong network of blood vessels essential for the lung to survive. There was no evidence of pulmonary edema, the build of fluid in the lungs, which is usually a sign of the blood vessels not working efficiently.  There was no sign of rejection of the transplanted organs, and the pigs were healthy up to the point where they were euthanized.

One lingering concern is how well the bio-engineered lungs delivered oxygen. The four pigs who received the trasplant [sic] had one original functioning lung, so they didn’t depend on their new bio-engineered lung for breathing. The scientists were not sure that the bio-engineered lung was mature enough to handle the full load of oxygen on its own.

You can hear Bob McDonald’s (host of Quirks & Quarks, a Canadian Broadcasting Corporation science radio programme) interview lead scientist, Dr. Joan Nichols if you go to here. (Note: I find he overmodulates his voice but some may find he has a ‘friendly’ voice.)

This is an image of the lung scaffold produced by the team,

Lung scaffold in the bioreactor chamber on Day 1 of the experiment, before the cells from the study pig were added. (Credit: Joan Nichols) [downloaded from https://www.cbc.ca/radio/quirks/dec-29-2018-water-on-mars-lab-grown-lungs-and-more-the-biggest-science-stories-of-2018-1.4940811/lab-grown-lungs-are-transplanted-in-pigs-today-they-may-help-humans-tomorrow-1.4940822]

Here’s more technical detail in an August 1, 2018i University of Texas Medical Branch (UTMB) news release (also on EurekAlert), which originally announced the research,

A research team at the University of Texas Medical Branch at Galveston have bioengineered lungs and transplanted them into adult pigs with no medical complication.

In 2014, Joan Nichols and Joaquin Cortiella from The University of Texas Medical Branch at Galveston were the first research team to successfully bioengineer human lungs in a lab. In a paper now available in Science Translational Medicine, they provide details of how their work has progressed from 2014 to the point no complications have occurred in the pigs as part of standard preclinical testing.

“The number of people who have developed severe lung injuries has increased worldwide, while the number of available transplantable organs have decreased,” said Cortiella, professor of pediatric anesthesia. “Our ultimate goal is to eventually provide new options for the many people awaiting a transplant,” said Nichols, professor of internal medicine and associate director of the Galveston National Laboratory at UTMB.

To produce a bioengineered lung, a support scaffold is needed that meets the structural needs of a lung. A support scaffold was created using a lung from an unrelated animal that was treated using a special mixture of sugar and detergent to eliminate all cells and blood in the lung, leaving only the scaffolding proteins or skeleton of the lung behind. This is a lung-shaped scaffold made totally from lung proteins.

The cells used to produce each bioengineered lung came from a single lung removed from each of the study animals. This was the source of the cells used to produce a tissue-matched bioengineered lung for each animal in the study. The lung scaffold was placed into a tank filled with a carefully blended cocktail of nutrients and the animals’ own cells were added to the scaffold following a carefully designed protocol or recipe. The bioengineered lungs were grown in a bioreactor for 30 days prior to transplantation. Animal recipients were survived for 10 hours, two weeks, one month and two months after transplantation, allowing the research team to examine development of the lung tissue following transplantation and how the bioengineered lung would integrate with the body.

All of the pigs that received a bioengineered lung stayed healthy. As early as two weeks post-transplant, the bioengineered lung had established the strong network of blood vessels needed for the lung to survive.

“We saw no signs of pulmonary edema, which is usually a sign of the vasculature not being mature enough,” said Nichols and Cortiella. “The bioengineered lungs continued to develop post-transplant without any infusions of growth factors, the body provided all of the building blocks that the new lungs needed.”

Nichols said that the focus of the study was to learn how well the bioengineered lung adapted and continued to mature within a large, living body. They didn’t evaluate how much the bioengineered lung provided oxygenation to the animal.

“We do know that the animals had 100 percent oxygen saturation, as they had one normal functioning lung,” said Cortiella. “Even after two months, the bioengineered lung was not yet mature enough for us to stop the animal from breathing on the normal lung and switch to just the bioengineered lung.”

For this reason, future studies will look at long-term survival and maturation of the tissues as well as gas exchange capability.

The researchers said that with enough funding, they could grow lungs to transplant into people in compassionate use circumstances within five to 10 years.

“It has taken a lot of heart and 15 years of research to get us this far, our team has done something incredible with a ridiculously small budget and an amazingly dedicated group of people,” Nichols and Cortiella said.

Here’s a citation and another link for the paper,

Production and transplantation of bioengineered lung into a large-animal model by Joan E. Nichols, Saverio La Francesca, Jean A. Niles, Stephanie P. Vega, Lissenya B. Argueta, Luba Frank, David C. Christiani, Richard B. Pyles, Blanca E. Himes, Ruyang Zhang, Su Li, Jason Sakamoto, Jessica Rhudy, Greg Hendricks, Filippo Begarani, Xuewu Liu, Igor Patrikeev, Rahul Pal, Emiliya Usheva, Grace Vargas, Aaron Miller, Lee Woodson, Adam Wacher, Maria Grimaldo, Daniil Weaver, Ron Mlcak, and Joaquin Cortiella. Science Translational Medicine 01 Aug 2018: Vol. 10, Issue 452, eaao3926 DOI: 10.1126/scitranslmed.aao3926

This paper is behind a paywall.

Artificial lung cancer tissue

The research teams at the University of Toronto and the University of Ottawa worked on creating artificial lung tissue but other applications are possible too. First, there’s the announcement in a February 25, 2019 news item on phys.org,

A 3-D hydrogel created by researchers in U of T Engineering Professor Molly Shoichet’s lab is helping University of Ottawa researchers to quickly screen hundreds of potential drugs for their ability to fight highly invasive cancers.

Cell invasion is a critical hallmark of metastatic cancers, such as certain types of lung and brain cancer. Fighting these cancers requires therapies that can both kill cancer cells as well as prevent cell invasion of healthy tissue. Today, most cancer drugs are only screened for their ability to kill cancer cells.

“In highly invasive diseases, there is a crucial need to screen for both of these functions,” says Shoichet. “We now have a way to do this.”

A February 25, 2019 University of Toronto news release (also on EurekAlert), which originated the news item, offers more detail ,

In their latest research, the team used hydrogels to mimic the environment of lung cancer, selectively allowing cancer cells, and not healthy cells, to invade. In their latest research, the team used hydrogels to mimic the environment of lung cancer, selectively allowing cancer cells, and not healthy cells, to invade. This emulated environment enabled their collaborators in Professor Bill Stanford’s lab at University of Ottawa to screen for both cancer-cell growth and invasion. The study, led by Roger Y. Tam, a research associate in Shochet’s lab, was recently published in Advanced Materials.

“We can conduct this in a 384-well plate, which is no bigger than your hand. And with image-analysis software, we can automate this method to enable quick, targeted screenings for hundreds of potential cancer treatments,” says Shoichet.

One example is the researchers’ drug screening for lymphangioleiomyomatosis (LAM), a rare lung disease affecting women. Shoichet and her team were inspired by the work of Green Eggs and LAM, a Toronto-based organization raising awareness of the disease.

Using their hydrogels, they were able to automate and screen more than 800 drugs, thereby uncovering treatments that could target disease growth and invasion.

In the ongoing collaboration, the researchers plan to next screen multiple drugs at different doses to gain greater insight into new treatment methods for LAM. The strategies and insights they gain could also help identify new drugs for other invasive cancers.

Shoichet, who was recently named a Distinguished Woman in Chemistry or Chemical Engineering, also plans to patent the hydrogel technology.

“This has, and continues to be, a great collaboration that is advancing knowledge at the intersection of engineering and biology,” says Shoichet.

I note that Shoichet (pronounced ShoyKet) is getting ready to patent this work. I do have a question about this and it’s not up to Shoichet to answer as she didn’t create the system. Will the taxpayers who funded her work receive any financial benefits should the hydrogel prove to be successful or will we be paying double, both supporting her research and paying for the hydrogel through our healthcare costs?

Getting back to the research, here’s a link to and a citation for the paper,

Rationally Designed 3D Hydrogels Model Invasive Lung Diseases Enabling High‐Content Drug Screening by Roger Y. Tam, Julien Yockell‐Lelièvre, Laura J. Smith, Lisa M. Julian, Alexander E. G. Baker, Chandarong Choey, Mohamed S. Hasim, Jim Dimitroulakos, William L. Stanford, Molly S. Shoichet. Advanced Materials Volume 31, Issue 7 February 15, 2019 1806214 First published online: 27 December 2018 DOI: https://doi.org/10.1002/adma.201806214

This paper is behind a paywall.

A 3D printed eye cornea and a 3D printed copy of your brain (also: a Brad Pitt connection)

Sometimes it’s hard to keep up with 3D tissue printing news. I have two news bits, one concerning eyes and another concerning brains.

3D printed human corneas

A May 29, 2018 news item on ScienceDaily trumpets the news,

The first human corneas have been 3D printed by scientists at Newcastle University, UK.

It means the technique could be used in the future to ensure an unlimited supply of corneas.

As the outermost layer of the human eye, the cornea has an important role in focusing vision.

Yet there is a significant shortage of corneas available to transplant, with 10 million people worldwide requiring surgery to prevent corneal blindness as a result of diseases such as trachoma, an infectious eye disorder.

In addition, almost 5 million people suffer total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease.

The proof-of-concept research, published today [May 29, 2018] in Experimental Eye Research, reports how stem cells (human corneal stromal cells) from a healthy donor cornea were mixed together with alginate and collagen to create a solution that could be printed, a ‘bio-ink’.

Here are the proud researchers with their cornea,

Caption: Dr. Steve Swioklo and Professor Che Connon with a dyed cornea. Credit: Newcastle University, UK

A May 30,2018 Newcastle University press release (also on EurekAlert but published on May 29, 2018), which originated the news item, adds more details,

Using a simple low-cost 3D bio-printer, the bio-ink was successfully extruded in concentric circles to form the shape of a human cornea. It took less than 10 minutes to print.

The stem cells were then shown to culture – or grow.

Che Connon, Professor of Tissue Engineering at Newcastle University, who led the work, said: “Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

“Our unique gel – a combination of alginate and collagen – keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer.

“This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.”

The scientists, including first author and PhD student Ms Abigail Isaacson from the Institute of Genetic Medicine, Newcastle University, also demonstrated that they could build a cornea to match a patient’s unique specifications.

The dimensions of the printed tissue were originally taken from an actual cornea. By scanning a patient’s eye, they could use the data to rapidly print a cornea which matched the size and shape.

Professor Connon added: “Our 3D printed corneas will now have to undergo further testing and it will be several years before we could be in the position where we are using them for transplants.

“However, what we have shown is that it is feasible to print corneas using coordinates taken from a patient eye and that this approach has potential to combat the world-wide shortage.”

Here’s a link to and a citation for the paper,

3D bioprinting of a corneal stroma equivalent by Abigail Isaacson, Stephen Swioklo, Che J. Connon. Experimental Eye Research Volume 173, August 2018, Pages 188–193 and 2018 May 14 pii: S0014-4835(18)30212-4. doi: 10.1016/j.exer.2018.05.010. [Epub ahead of print]

This paper is behind a paywall.

A 3D printed copy of your brain

I love the title for this May 30, 2018 Wyss Institute for Biologically Inspired Engineering news release: Creating piece of mind by Lindsay Brownell (also on EurekAlert),

What if you could hold a physical model of your own brain in your hands, accurate down to its every unique fold? That’s just a normal part of life for Steven Keating, Ph.D., who had a baseball-sized tumor removed from his brain at age 26 while he was a graduate student in the MIT Media Lab’s Mediated Matter group. Curious to see what his brain actually looked like before the tumor was removed, and with the goal of better understanding his diagnosis and treatment options, Keating collected his medical data and began 3D printing his MRI [magnetic resonance imaging] and CT [computed tomography] scans, but was frustrated that existing methods were prohibitively time-intensive, cumbersome, and failed to accurately reveal important features of interest. Keating reached out to some of his group’s collaborators, including members of the Wyss Institute at Harvard University, who were exploring a new method for 3D printing biological samples.

“It never occurred to us to use this approach for human anatomy until Steve came to us and said, ‘Guys, here’s my data, what can we do?” says Ahmed Hosny, who was a Research Fellow with at the Wyss Institute at the time and is now a machine learning engineer at the Dana-Farber Cancer Institute. The result of that impromptu collaboration – which grew to involve James Weaver, Ph.D., Senior Research Scientist at the Wyss Institute; Neri Oxman, [emphasis mine] Ph.D., Director of the MIT Media Lab’s Mediated Matter group and Associate Professor of Media Arts and Sciences; and a team of researchers and physicians at several other academic and medical centers in the US and Germany – is a new technique that allows images from MRI, CT, and other medical scans to be easily and quickly converted into physical models with unprecedented detail. The research is reported in 3D Printing and Additive Manufacturing.

“I nearly jumped out of my chair when I saw what this technology is able to do,” says Beth Ripley, M.D. Ph.D., an Assistant Professor of Radiology at the University of Washington and clinical radiologist at the Seattle VA, and co-author of the paper. “It creates exquisitely detailed 3D-printed medical models with a fraction of the manual labor currently required, making 3D printing more accessible to the medical field as a tool for research and diagnosis.”

Imaging technologies like MRI and CT scans produce high-resolution images as a series of “slices” that reveal the details of structures inside the human body, making them an invaluable resource for evaluating and diagnosing medical conditions. Most 3D printers build physical models in a layer-by-layer process, so feeding them layers of medical images to create a solid structure is an obvious synergy between the two technologies.

However, there is a problem: MRI and CT scans produce images with so much detail that the object(s) of interest need to be isolated from surrounding tissue and converted into surface meshes in order to be printed. This is achieved via either a very time-intensive process called “segmentation” where a radiologist manually traces the desired object on every single image slice (sometimes hundreds of images for a single sample), or an automatic “thresholding” process in which a computer program quickly converts areas that contain grayscale pixels into either solid black or solid white pixels, based on a shade of gray that is chosen to be the threshold between black and white. However, medical imaging data sets often contain objects that are irregularly shaped and lack clear, well-defined borders; as a result, auto-thresholding (or even manual segmentation) often over- or under-exaggerates the size of a feature of interest and washes out critical detail.

The new method described by the paper’s authors gives medical professionals the best of both worlds, offering a fast and highly accurate method for converting complex images into a format that can be easily 3D printed. The key lies in printing with dithered bitmaps, a digital file format in which each pixel of a grayscale image is converted into a series of black and white pixels, and the density of the black pixels is what defines the different shades of gray rather than the pixels themselves varying in color.

Similar to the way images in black-and-white newsprint use varying sizes of black ink dots to convey shading, the more black pixels that are present in a given area, the darker it appears. By simplifying all pixels from various shades of gray into a mixture of black or white pixels, dithered bitmaps allow a 3D printer to print complex medical images using two different materials that preserve all the subtle variations of the original data with much greater accuracy and speed.

The team of researchers used bitmap-based 3D printing to create models of Keating’s brain and tumor that faithfully preserved all of the gradations of detail present in the raw MRI data down to a resolution that is on par with what the human eye can distinguish from about 9-10 inches away. Using this same approach, they were also able to print a variable stiffness model of a human heart valve using different materials for the valve tissue versus the mineral plaques that had formed within the valve, resulting in a model that exhibited mechanical property gradients and provided new insights into the actual effects of the plaques on valve function.

“Our approach not only allows for high levels of detail to be preserved and printed into medical models, but it also saves a tremendous amount of time and money,” says Weaver, who is the corresponding author of the paper. “Manually segmenting a CT scan of a healthy human foot, with all its internal bone structure, bone marrow, tendons, muscles, soft tissue, and skin, for example, can take more than 30 hours, even by a trained professional – we were able to do it in less than an hour.”

The researchers hope that their method will help make 3D printing a more viable tool for routine exams and diagnoses, patient education, and understanding the human body. “Right now, it’s just too expensive for hospitals to employ a team of specialists to go in and hand-segment image data sets for 3D printing, except in extremely high-risk or high-profile cases. We’re hoping to change that,” says Hosny.

In order for that to happen, some entrenched elements of the medical field need to change as well. Most patients’ data are compressed to save space on hospital servers, so it’s often difficult to get the raw MRI or CT scan files needed for high-resolution 3D printing. Additionally, the team’s research was facilitated through a joint collaboration with leading 3D printer manufacturer Stratasys, which allowed access to their 3D printer’s intrinsic bitmap printing capabilities. New software packages also still need to be developed to better leverage these capabilities and make them more accessible to medical professionals.

Despite these hurdles, the researchers are confident that their achievements present a significant value to the medical community. “I imagine that sometime within the next 5 years, the day could come when any patient that goes into a doctor’s office for a routine or non-routine CT or MRI scan will be able to get a 3D-printed model of their patient-specific data within a few days,” says Weaver.

Keating, who has become a passionate advocate of efforts to enable patients to access their own medical data, still 3D prints his MRI scans to see how his skull is healing post-surgery and check on his brain to make sure his tumor isn’t coming back. “The ability to understand what’s happening inside of you, to actually hold it in your hands and see the effects of treatment, is incredibly empowering,” he says.

“Curiosity is one of the biggest drivers of innovation and change for the greater good, especially when it involves exploring questions across disciplines and institutions. The Wyss Institute is proud to be a space where this kind of cross-field innovation can flourish,” says Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).

Here’s an image illustrating the work,

Caption: This 3D-printed model of Steven Keating’s skull and brain clearly shows his brain tumor and other fine details thanks to the new data processing method pioneered by the study’s authors. Credit: Wyss Institute at Harvard University

Here’s a link to and a citation for the paper,

From Improved Diagnostics to Presurgical Planning: High-Resolution Functionally Graded Multimaterial 3D Printing of Biomedical Tomographic Data Sets by Ahmed Hosny , Steven J. Keating, Joshua D. Dilley, Beth Ripley, Tatiana Kelil, Steve Pieper, Dominik Kolb, Christoph Bader, Anne-Marie Pobloth, Molly Griffin, Reza Nezafat, Georg Duda, Ennio A. Chiocca, James R.. Stone, James S. Michaelson, Mason N. Dean, Neri Oxman, and James C. Weaver. 3D Printing and Additive Manufacturing http://doi.org/10.1089/3dp.2017.0140 Online Ahead of Print:May 29, 2018

This paper appears to be open access.

A tangential Brad Pitt connection

It’s a bit of Hollywood gossip. There was some speculation in April 2018 that Brad Pitt was dating Dr. Neri Oxman highlighted in the Wyss Institute news release. Here’s a sample of an April 13, 2018 posting on Laineygossip (Note: A link has been removed),

It took him a long time to date, but he is now,” the insider tells PEOPLE. “He likes women who challenge him in every way, especially in the intellect department. Brad has seen how happy and different Amal has made his friend (George Clooney). It has given him something to think about.”

While a Pitt source has maintained he and Oxman are “just friends,” they’ve met up a few times since the fall and the insider notes Pitt has been flying frequently to the East Coast. He dropped by one of Oxman’s classes last fall and was spotted at MIT again a few weeks ago.

Pitt and Oxman got to know each other through an architecture project at MIT, where she works as a professor of media arts and sciences at the school’s Media Lab. Pitt has always been interested in architecture and founded the Make It Right Foundation, which builds affordable and environmentally friendly homes in New Orleans for people in need.

“One of the things Brad has said all along is that he wants to do more architecture and design work,” another source says. “He loves this, has found the furniture design and New Orleans developing work fulfilling, and knows he has a talent for it.”

It’s only been a week since Page Six first broke the news that Brad and Dr Oxman have been spending time together.

I’m fascinated by Oxman’s (and her colleagues’) furniture. Rose Brook writes about one particular Oxman piece in her March 27, 2014 posting for TCT magazine (Note: Links have been removed),

MIT Professor and 3D printing forerunner Neri Oxman has unveiled her striking acoustic chaise longue, which was made using Stratasys 3D printing technology.

Oxman collaborated with Professor W Craig Carter and Composer and fellow MIT Professor Tod Machover to explore material properties and their spatial arrangement to form the acoustic piece.

Christened Gemini, the two-part chaise was produced using a Stratasys Objet500 Connex3 multi-colour, multi-material 3D printer as well as traditional furniture-making techniques and it will be on display at the Vocal Vibrations exhibition at Le Laboratoire in Paris from March 28th 2014.

An Architect, Designer and Professor of Media, Arts and Science at MIT, Oxman’s creation aims to convey the relationship of twins in the womb through material properties and their arrangement. It was made using both subtractive and additive manufacturing and is part of Oxman’s ongoing exploration of what Stratasys’ ground-breaking multi-colour, multi-material 3D printer can do.

Brook goes on to explain how the chaise was made and the inspiration that led to it. Finally, it’s interesting to note that Oxman was working with Stratasys in 2014 and that this 2018 brain project is being developed in a joint collaboration with Statasys.

That’s it for 3D printing today.

Repairing a ‘broken’ heart with a 3D printed patch

The idea of using stem cells to help heal your heart so you don’t have scar tissue seems to be a step closer to reality. From an April 14, 2017 news item on ScienceDaily which announces the research and explains why scar tissue in your heart is a problem,

A team of biomedical engineering researchers, led by the University of Minnesota, has created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack.

According to the American Heart Association, heart disease is the No. 1 cause of death in the U.S. killing more than 360,000 people a year. During a heart attack, a person loses blood flow to the heart muscle and that causes cells to die. Our bodies can’t replace those heart muscle cells so the body forms scar tissue in that area of the heart, which puts the person at risk for compromised heart function and future heart failure.

An April 13, 2017 University of Minnesota news release (also on EurekAlert but dated April 14, 2017), which originated the news item, describes the work in more detail,

In this study, researchers from the University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries.

“This is a significant step forward in treating the No. 1 cause of death in the U.S.,” said Brenda Ogle, an associate professor of biomedical engineering at the University of Minnesota. “We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years.”

Ogle said that this research is different from previous research in that the patch is modeled after a digital, three-dimensional scan of the structural proteins of native heart tissue.  The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells.  Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue.

“We were quite surprised by how well it worked given the complexity of the heart,” Ogle said.  “We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch.”

Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart.

The researchers has made this video of beating heart cells in a petri dish available,

Date: Published on Apr 14, 2017

Caption: Researchers used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab. Credit: Brenda Ogle, University of Minnesota

Here’s a link to and a citation for the paper,

Myocardial Tissue Engineering With Cells Derived From Human-Induced Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold by Ling Gao, Molly E. Kupfer, Jangwook P. Jung, Libang Yang, Patrick Zhang, Yong Da Sie, Quyen Tran, Visar Ajeti, Brian T. Freeman, Vladimir G. Fast, Paul J. Campagnola, Brenda M. Ogle, Jianyi Zhang. Circulation Research April 14, 2017, Volume 120, Issue 8 https://doi.org/10.1161/CIRCRESAHA.116.310277 Circulation Research. 2017;120:1318-1325 Originally published online] January 9, 2017

This paper appears to be open access.

A new platform for culturing stem cells: a Multiplexed Artificial Cellular Microenvironment array

Japanese scientists have developed a more precise method for culturing stem cells according to a March 14, 2017 news item on Nanowerk,

A team of researchers in Japan has developed a new platform for culturing human pluripotent stem cells that provides far more control of culture conditions than previous tools by using micro and nanotechnologies.

The Multiplexed Artificial Cellular Microenvironment (MACME) array places nanofibres, mimicking cellular matrices, into fluid-filled micro-chambers of precise sizes, which mimic extracellular environments.

Caption: The Multiplexed Artificial Cellular Microenvironment (MACME) array, consisted with a microfluidic structure and nanofibre array for mimicking cellular microenvironments. Credit: Kyoto University iCeMS

A March 17, 2017 Kyoto University press release (also on EurekAlert), which originated the news item, explains the research in more detail,

Human pluripotent stems cells (hPSCs) hold great promise for tissue engineering, regenerative medicine and cell-based therapies because they can become any type of cell. The environment surrounding the cells plays a major role in determining what tissues they become, if they replicate into more cells, or die. However, understanding these interactions has been difficult because researchers have lacked tools that work on the appropriate scale.

Often, stem cells are cultured in a cell culture medium in small petri dishes. While factors such as medium pH levels and nutrients can be controlled, the artificial set up is on the macroscopic scale and does not allow for precise control of the physical environment surrounding the cells.

The MACME array miniaturizes this set up, culturing stem cells in rows of micro-chambers of cell culture medium. It also takes it a step further by placing nanofibers in these chambers to mimic the structures found around cells.

Led by Ken-ichiro Kamei of Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS), the team tested a variety of nanofiber materials and densities, micro-chamber heights and initial stem cell densities to determine the best combination that encourages human pluripotent stem cells to replicate.

They stained the cells with several fluorescent markers and used a microscope to see if the cells died, replicated or differentiated into tissues.

Their analysis revealed that gelatin nanofibers and medium-sized chambers that create medium seed cell density provided the best environment for the stem cells to continue to multiply. The quantity and density of neighboring cells strongly influences cell survival.

The array is an “optimal and powerful approach for understanding how environmental cues regulate cellular functions,” the researchers conclude in a recently published paper in the journal Small.

This array appears to be the first time multiple kinds of extracellular environments can be mounted onto a single device, making it much easier to compare how different environments influence cells.

The MACME array could substantially reduce experiment costs compared to conventional tools, in part because it is low volume and requires less cell culture medium. The array does not require any special equipment and is compatible with both commonly used laboratory pipettes and automated pipette systems for performing high-throughput screening.

Here’s a link to and a citation for the paper,

Microfluidic-Nanofiber Hybrid Array for Screening of Cellular Microenvironments by Ken-ichiro Kamei, Yasumasa Mashimo, Momoko Yoshioka, Yumie Tokunaga, Christopher Fockenberg, Shiho Terada, Yoshie Koyama, Minako Nakajima, Teiko Shibata-Seki, Li Liu, Toshihiro Akaike, Eiry Kobatake, Siew-Eng How, Motonari Uesugi, and Yong Chen. Small DOI: 10.1002/smll.201603104 Version of Record online: 8 MAR 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

York University (Toronto, Ontario, Canada) research team creates 3D beating heart and matters of the heart at the Ontario Institute for Regenerative Medicine

I have two items about cardiac research in Ontario. Not strictly speaking about nanotechnology, the two items do touch on topics covered here before, 3D organs and stem cells.

York University and its 3D beating heart

A Feb. 9, 2017 York University news release (also on EurekAlert), describe an innovative approach to creating 3D heart tissue,

Matters of the heart can be complicated, but York University scientists have found a way to create 3D heart tissue that beats in synchronized harmony, like a heart in love, that will lead to better understanding of cardiac health, and improved treatments.

York U chemistry Professor Muhammad Yousaf and his team of grad students have devised a way to stick three different types of cardiac cells together, like Velcro, to make heart tissue that beats as one.

Until now, most 2D and 3D in vitro tissue did not beat in harmony and required scaffolding for the cells to hold onto and grow, causing limitations. In this research, Yousaf and his team made a scaffold free beating tissue out of three cell types found in the heart – contractile cardiac muscle cells, connective tissue cells and vascular cells.

The researchers believe this is the first 3D in vitro cardiac tissue with three cell types that can beat together as one entity rather than at different intervals.

“This breakthrough will allow better and earlier drug testing, and potentially eliminate harmful or toxic medications sooner,” said Yousaf of York U’s Faculty of Science.

In addition, the substance used to stick cells together (ViaGlue), will provide researchers with tools to create and test 3D in vitro cardiac tissue in their own labs to study heart disease and issues with transplantation. Cardiovascular associated diseases are the leading cause of death globally and are responsible for 40 per cent of deaths in North America.

“Making in vitro 3D cardiac tissue has long presented a challenge to scientists because of the high density of cells and muscularity of the heart,” said Dmitry Rogozhnikov, a chemistry PhD student at York. “For 2D or 3D cardiac tissue to be functional it needs the same high cellular density and the cells must be in contact to facilitate synchronized beating.”

Although the 3D cardiac tissue was created at a millimeter scale, larger versions could be made, said Yousaf, who has created a start-up company OrganoLinX to commercialize the ViaGlue reagent and to provide custom 3D tissues on demand.

Here’s a link to and a citation for the paper,

Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering by Dmitry Rogozhnikov, Paul J. O’Brien, Sina Elahipanah, & Muhammad N. Yousaf. Scientific Reports 6, Article number: 39806 (2016) doi:10.1038/srep39806 Published online: 23 December 2016

This paper is open access.

Ontario Institute for Regenerative Medicine and its heart stem cell research

Steven Erwood has written about how Toronto has become a centre for certain kinds of cardiac research by focusing on specific researchers in a Feb. 13, 2017 posting on the Ontario Institute for Regenerative Medicine’s expression blog (Note: Links have been removed),

You may have heard that Paris is the city of love, but you might not know that Toronto specializes in matters of the heart, particularly broken hearts.

Dr. Ren Ke Li, an investigator with the Ontario Institute for Regenerative Medicine, established his lab at the Toronto General Hospital Research Institute in 1993 hoping to find a way to replace the muscle cells, or cardiomyocytes, that are lost after a heart attack. Specifically, Li hoped to transplant a collection of cells, called stem cells, into a heart damaged by a heart attack. Stem cells have the power to differentiate into virtually any cell type, so if Li could coax them to become cardiomyocytes, they could theoretically reverse the damage caused by the heart attack.

Over the years, Li’s experiments using stem cells to regenerate and repair damaged heart tissue, which progressed all the way through to human clinical trials, pushed Li to rethink his approach to heart repair. Most of the transplanted cells failed to engraft to the host tissue and many of those that did successfully integrate into the patient’s heart remained non-contractile, sitting still beside the rest of the beating heart muscle. Despite this, the treatments were still proving beneficial — albeit less beneficial than Li had hoped. These cells weren’t replacing the lost cardiomyocytes, but they were still helping the patient recover. Li was then just beginning to reveal something that is now well described: transplanting exogenous stem cells (originating outside the patient) onto damaged tissue stimulated the endogenous stem cells to repair that damage. These transplanted stem cells were changing the behaviour of the patient’s own stem cells, enhancing their response to injury.

Li calls this process “rejuvenation” — arguing that the reason older populations can’t recover from cardiac injury is because they have fewer stem cells, and those stem cells have lost their ability to repair and regenerate damaged tissue over time. Li argues that the positive effects he was seeing in his experiments and clinical trials was a restoration or reversal of age-related deterioration in repair capability — a rejuvenation of the aged heart.

Li, alongside fellow OIRM [Ontario Institute for Regenerative Medicine] researcher and cardiac surgeon at Toronto General Hospital, Dr. Richard Weisel, dedicated a large part of their research effort to understanding this process. Weisel explains, “We put young cells into old animals, and we can get them to respond to a heart attack like a young person — which is remarkable!”

A team of researchers led by the duo published an article in Basic Research in Cardiology last month describing a new method to rejuvenate the aged heart, and characterizing this rejuvenation at the molecular and cellular level.

Successfully advancing this research to the clinic is where Weisel thinks Toronto provides a unique advantage. “We have the ability to do the clinical trials — the same people who are working on these projects [in the lab], can also take them into the clinic, and a lot of other places in the world [the clinicians and the researchers] are separate. We’ve been doing that for all the areas of stem cell research.” This unique set of circumstances, Weisel argues, more readily allows for a successful transition from research to clinical practice.

But an integrated research and clinical environment isn’t all the city has to offer to those looking to make substantial progress in stem cell therapies. Dr. Michael Laflamme, OIRM researcher and a leading authority on stem cell therapies for cardiac repair, called his decision to relocate to Toronto from the University of Washington in Seattle “a no-brainer”.

Laflamme focuses on improving the existing approaches to exogenous stem cell transplantation in cardiac repair and believes that solving the problems Li faced in his early experiments is just a matter of finding the right cell type. Laflamme, in an ongoing preclinical trial funded by OIRM, is differentiating stem cells in a bioreactor into ventricular cardiomyocytes, the specific type of cell lost after a heart attack, and delivering those cells directly to the scar tissue in hopes of turning it back into muscle. Laflamme is optimistic these ventricular cardiomyocytes might be just the cell type he’s looking for. Using these cells in animal models, although in a mixture of other cardiac cell types, Laflamme explains, “We’ve shown that those cells will stably engraft and they actually become electrically integrated with the rest of the tissue — they will [beat] in synchrony with the rest of the heart.”

Laflamme states that “Toronto is the place where we can get this stuff done better and we can get it done faster,” citing the existing Toronto-based expertise in both the differentiation of stem cells and the biotechnological means to scale these processes as being unparalleled elsewhere in the world.

It’s not only academic researchers and clinicians that recognize Toronto’s potential to advance regenerative medicine and stem cell therapy. Pharmaceutical giant Bayer, partnered with San Francisco-based venture capital firm Versant Ventures, announced last December a USD 225 million investment in a stem cell biotechnology company called BlueRock Therapeutics — the second largest investment of it’s kind in the history of the biotechnology industry. …

There’s substantially to more Erwood’s piece in the original posting.

One final thought, I wonder if there is a possibility that York University’s ViaGlue might be useful in the work talking place at Ontario Institute for Regenerative Medicine. I realize the two institutions are in the same city but do the researchers even know about each other’s work?

Better technique for growing organoids taking them from the lab to the clinic

A Nov. 16, 2016 École Polytechnique Fédérale de Lausanne (EPFL) press release (also on EurekAlert) describes a new material for growing organoids,

Organoids are miniature organs that can be grown in the lab from a person’s stem cells. They can be used to model diseases, and in the future could be used to test drugs or even replace damaged tissue in patients. But currently organoids are very difficult to grow in a standardized and controlled way, which is key to designing and using them. EPFL scientists have now solved the problem by developing a patent-pending “hydrogel” that provides a fully controllable and tunable way to grow organoids. …

Organoids need a 3D scaffold

Growing organoids begins with stem cells — immature cells that can grow into any cell type of the human body and that play key roles in tissue function and regeneration. To form an organoid, the stem cells are grown inside three-dimensional gels that contain a mix of biomolecules that promote stem cell renewal and differentiation.

The role of these gels is to mimic the natural environment of the stem cells, which provides them with a protein- and sugar-rich scaffold called the “extracellular matrix”, upon which the stem cells build specific body tissues. The stem cells stick to the extracellular matrix gel, and then “self-organize” into miniature organs like retinas, kidneys, or the gut. These tiny organs retain key aspects of their real-life biology, and can be used to study diseases or test drugs before moving on to human trials.

But the current gels used for organoid growth are derived from mice, and have problems. First, it is impossible to control their makeup from batch to batch, which can cause stem cells to behave inconsistently. Second, their biochemical complexity makes them very difficult to fine-tune for studying the effect of different parameters (e.g. biological molecules, mechanical properties, etc.) on the growth of organoids. Finally, the gels can carry pathogens or immunogens, which means that they are not suitable for growing organoids to be used in the clinic.

A hydrogel solution

The lab of Matthias Lütolf at EPFL’s Institute of Bioengineering has developed a synthetic “hydrogel” that eschews the limitations of conventional, naturally derived gels. The patent-pending gel is made of water and polyethylene glycol, a substance used widely today in various forms, from skin creams and toothpastes to industrial applications and, as in this case, bioengineering.

Nikolce Gjorevski, the first author of the study, and his colleagues used the hydrogel to grow stem cells of the gut into a miniature intestine. The functional hydrogel was not only a goal in and of itself, but also a means to identify the factors that influence the stem cells’ ability to expand and form organoids. By carefully tweaking the hydrogel’s properties, they discovered that separate stages of the organoid formation process require different mechanical environments and biological components.

One such factor is a protein called fibronectin, which helps the stem cells attach to the hydrogel. Lütolf’s lab found that this attachment itself is immensely important for growing organoids, as it triggers a whole host of signals to the stem cell that tell it to grow and build an intestine-like structure. The researchers also discovered an essential role for the mechanical properties, i.e. the physical stiffness, of the gel in regulating intestinal stem cell behavior, shedding light on how cells are able to sense, process and respond to physical stimuli. This insight is particularly valuable – while the influence of biochemical signals on stem cells is well-understood, the effect of physical factors has been more mysterious.

Because the hydrogel is man-made, it is easy to control its chemical composition and key properties, and ensure consistency from batch to batch. And because it is artificial, it does not carry any risk of infection or triggering immune responses. As such, it provides a means of moving organoids from basic research to actual pharmaceutical and clinical applications in the future.

Lütolf’s lab is now researching other types of stem cells in order to extend the capacities of their hydrogel into other tissues.

Here’s a link to and a citation for the paper,

Designer matrices for intestinal stem cell and organoid culture by Nikolce Gjorevski, Norman Sachs, Andrea Manfrin, Sonja Giger, Maiia E. Bragina, Paloma Ordóñez-Morán, Hans Clevers, & Matthias P. Lutolf.  Nature (2016) doi:10.1038/nature20168 Published online 16 November 2016

This paper is behind a paywall.

A grant for regenerating bones with injectable stem cell microspheres

I have a longstanding interest in bones partly due to my introduction to a skeleton in a dance course and to US artist Georgia O’Keeffe’s paintings. In any event, it’s been too long since I’ve featured any research on bones here.

This news comes from the UK’s University of Nottingham. A July 25, 2016 news item on Nanowerk announced a grant for stem cell research,

The University of Nottingham has secured £1.2m to develop injectable stem cell-carrying materials to treat and prevent fractures caused by osteoporosis and other bone-thinning diseases.

A July 25, 2016 University of Nottingham press release, which originated the news item, offers more information about the proposed therapy and the research project (Note: Links have been removed),

The experimental materials consist of porous microspheres produced from calcium phosphates – a key component in bones – to be filled with stem cells extracted from the patient.

The targeted therapy could offer a quick, easy and minimally-invasive treatment that is injected into areas considered to be at high-risk of fracture to promote bone regeneration.

The funding grant, from the National Institute for Health Research (NIHR i4i Challenge Award), also supports the development of a prototype delivery device to inject these stem cell loaded microspheres to the sites of interest.

In addition, project partners will investigate how well the materials stay in place once they have been injected inside the body.

Research leads, Dr Ifty Ahmed and Professor Brigitte Scammell explained that the aim was to develop a preventive treatment option to address the growing issue of fractures occurring due to bone-thinning diseases, which is exacerbated due to the worldwide ageing population.

Osteoporosis-related conditions affect some three million Britons, and cost the NHS over £1.73bn each year, according to the National Osteoporotic Society.

Dr Ahmed, from the Faculty of Engineering at The University of Nottingham, said, “We would advocate a national screening program, using a DEXA scan, which measures bone mineral density, to identify people at high risk of fracture due to osteoporosis.

“If we could strengthen these peoples bone before they suffered from fractures, using a simple injection procedure, it would save people the pain and trauma of broken bones and associated consequences such as surgery and loss of independence.”

The NIHR grant will also fund a Patient and Public Involvement study on the suitability of the technology, gauging the opinions and personal experience of people affected by osteoporosis as sufferers or carers, for example.

The project has already undertaken proof-of-concept work to test the feasibility of manufacturing the microsphere materials and lab work to ensure that stem cells attach and reside within these novel microsphere carriers.

The research is still at an early stage and the project team are working towards next phase pre-clinical trials.

This work reminded me of an unfinished piece of science fiction where I developed a society that had the ability to grow bone to replace lost limbs, replace lost bone matter, and restructure faces. I should get back to it one of these days. In the meantime, here’s an image of a microsphere,

A close-up of a injectable stem-cell carrying microsphere made of calcium phosphate which are injected to prevent and treat fractures caused by bone-thinning diseases. (Image: Ifty Ahmed; University of Nottingham)

A close-up of a injectable stem-cell carrying microsphere made of calcium phosphate which are injected to prevent and treat fractures caused by bone-thinning diseases. (Image: Ifty Ahmed; University of Nottingham)

One final note, fragile bones are no joke but there does seem to be a movement to diagnose more and more people with osteoporosis. Alan Cassels, in his July/August 2016 article for Common Ground magazine, points out that the guidelines for diagnosis have changed and more healthy people are being targeted,

… Americans, the experts tell us, are suffering an epidemic of osteoporosis. A new US osteoporosis guideline says that 72% of women over 65 are considered ‘diseased’ – a number which rises to 93% for those over 75 years old – and hence in need of drug therapy.

What is going on here?

Clearly, the only real ‘epidemic’ is the growing phenomenon where risks for disease are being turned into diseases, in and of themselves. In this racket, ‘high’ blood pressure, elevated cholesterol, low bone density, fluctuating blood sugars, high eyeball pressure and low testosterone, among other things, become worrying signs of chronic, lifelong conditions that demand attention and medication. As I’ve said in the past, “If you want to know why pharma is increasingly targeting healthy people with ‘preventive medicine,’ it’s because that’s where the money is.”

One thing all these risks-as-disease models have in common is they are shaped and supported by clinical practice guidelines. In these guidelines, doctors are told to measure their patients’ parameters. If your measurements are outside some preset levels deemed ‘high risk’ by the expert guidelines, you know what that means: more frequent trips to the pharmacy. The main downside of guidelines is they slap labels on people who aren’t sick and instill in physicians the constant idea their healthy patients are really disease-ridden.

But this is a good news story and if you haven’t sensed it, there’s a rising backlash against medical guidelines, mostly led by doctors, researchers and even some patients outraged at what they see going on. …

I don’t wish to generalize from the situation in the US to the situation in the UK. The medical systems and models are quite different but since at least some of my readership is from the US, I thought this digression might prove helpful. Regardless of where you live, it never hurts to ask questions.

Online art/science exhibit on stem cells and Canadians, Dr. Jim Till and Dr. Ernest McCulloch

Before getting to the exhibit, here’s some background information from Stacey Johnson’s July 22, 2016 posting on the Signals blog (Note: Links have been removed),

You would be hard-pressed to find a Canadian stem cell scientist who doesn’t know that Drs. Jim Till and Ernest McCulloch advanced medical research across the globe with their discovery, in 1961, of blood stem cells at Toronto’s Princess Margaret Hospital, today the Princess Margaret Cancer Centre.

Recently, a group of artists, doctors, scientists and educators launched an art exhibit based on Till and McCulloch. The group, NASCENT Art Science Collective, created portraits of the two men, produced drawings and designed banners to honour these pioneers and their ground-breaking work.

You can find the show, The Protean SELF here. Before clicking on the link I encourage you to read Johnson’s piece in its entirety. Whether you choose to read it further or not, I highly (!) recommend that you scroll down the exhibit page or click on Interpretive Guide for Museum of Health Care before when viewing the images and text otherwise it will seem a hodgepodge. The guide was for the real life exhibit, which is over.

The guide won’t answer all your questions but will help greatly to contextualize the images and the text. For example,

Hanging in the main windows are two banners by Elizabeth Greisman. Elizabeth has been extending her work on stem cells, their discovery by Dr. James Till and the importance of “ah hah’ moments to the field of dance. Elizabeth has worked with the National Ballet – cross fertilization through this work has expanded her understanding of the two defining features of stem cells – the ability to regenerate and the ability to differentiate.

That description applies to this image (I believe),

Artist: Elizabeth Greisman

Artist: Elizabeth Greisman

It’s also very helpful for understanding why there’s a fair chunk text devoted to open access,

On entering the museum, you will find a banner with an original written piece by Dr. James Till, produced for this show. Dr. Till has become a tireless advocate for Open Access. His words speak for themselves.

Artist: Dr. James Till. Formatted by Wendy Wobeser

Artist: Dr. James Till. Formatted by Wendy Wobeser

Enjoy!

Replicating brain’s neural networks with 3D nanoprinting

An announcement about European Union funding for a project to reproduce neural networks by 3D nanoprinting can be found in a June 10, 2016 news item on Nanowerk,

The MESO-BRAIN consortium has received a prestigious award of €3.3million in funding from the European Commission as part of its Future and Emerging Technology (FET) scheme. The project aims to develop three-dimensional (3D) human neural networks with specific biological architecture, and the inherent ability to interrogate the network’s brain-like activity both electrophysiologically and optically. It is expected that the MESO-BRAIN will facilitate a better understanding of human disease progression, neuronal growth and enable the development of large-scale human cell-based assays to test the modulatory effects of pharmacological and toxicological compounds on neural network activity. The use of more physiologically relevant human models will increase drug screening efficiency and reduce the need for animal testing.

A June 9, 2016 Institute of Photonic Sciences (ICFO) press release (also on EurekAlert), which originated the news item, provides more detail,

About the MESO-BRAIN project

The MESO-BRAIN project’s cornerstone will use human induced pluripotent stem cells (iPSCs) that have been differentiated into neurons upon a defined and reproducible 3D scaffold to support the development of human neural networks that emulate brain activity. The structure will be based on a brain cortical module and will be unique in that it will be designed and produced using nanoscale 3D-laser-printed structures incorporating nano-electrodes to enable downstream electrophysiological analysis of neural network function. Optical analysis will be conducted using cutting-edge light sheet-based, fast volumetric imaging technology to enable cellular resolution throughout the 3D network. The MESO-BRAIN project will allow for a comprehensive and detailed investigation of neural network development in health and disease.

Prof Edik Rafailov, Head of the MESO-BRAIN project (Aston University) said: “What we’re proposing to achieve with this project has, until recently, been the stuff of science fiction. Being able to extract and replicate neural networks from the brain through 3D nanoprinting promises to change this. The MESO-BRAIN project has the potential to revolutionise the way we are able to understand the onset and development of disease and discover treatments for those with dementia or brain injuries. We cannot wait to get started!”

The MESO-BRAIN project will launch in September 2016 and research will be conducted over three years.

About the MESO-BRAIN consortium

Each of the consortium partners have been chosen for the highly specific skills & knowledge that they bring to this project. These include technologies and expertise in stem cells, photonics, physics, 3D nanoprinting, electrophysiology, molecular biology, imaging and commercialisation.

Aston University (UK) Aston Institute of Photonic Technologies (School of Engineering and Applied Science) is one of the largest photonic groups in UK and an internationally recognised research centre in the fields of lasers, fibre-optics, high-speed optical communications, nonlinear and biomedical photonics. The Cell & Tissue Biomedical Research Group (Aston Research Centre for Healthy Ageing) combines collective expertise in genetic manipulation, tissue engineering and neuronal modelling with the electrophysiological and optical analysis of human iPSC-derived neural networks. Axol Bioscience Ltd. (UK) was founded to fulfil the unmet demand for high quality, clinically relevant human iPSC-derived cells for use in biomedical research and drug discovery. The Laser Zentrum Hannover (Germany) is a leading research organisation in the fields of laser development, material processing, laser medicine, and laser-based nanotechnologies. The Neurophysics Group (Physics Department) at University of Barcelona (Spain) are experts in combing experiments with theoretical and computational modelling to infer functional connectivity in neuronal circuits. The Institute of Photonic Sciences (ICFO) (Spain) is a world-leading research centre in photonics with expertise in several microscopy techniques including light sheet imaging. KITE Innovation (UK) helps to bridge the gap between the academic and business sectors in supporting collaboration, enterprise, and knowledge-based business development.

For anyone curious about the FET funding scheme, there’s this from the press release,

Horizon 2020 aims to ensure Europe produces world-class science by removing barriers to innovation through funding programmes such as the FET. The FET (Open) funds forward-looking collaborations between advanced multidisciplinary science and cutting-edge engineering for radically new future technologies. The published success rate is below 1.4%, making it amongst the toughest in the Horizon 2020 suite of funding schemes. The MESO-BRAIN proposal scored a perfect 5/5.

You can find out more about the MESO-BRAIN project on its ICFO webpage.

They don’t say anything about it but I can’t help wondering if the scientists aren’t also considering the possibility of creating an artificial brain.

Cell-to-cell communication via nanotubes

It turns out that the cells communicating with each other are located in fruit flies. So, it’s perhaps not quite as exciting as one might have imagined, nonetheless, a July 1, 2015 news item on ScienceDaily provides some intriguing insights into cell communication,

When it comes to communicating with each other, some cells may be more “old school” than was previously thought.

Certain types of stem cells use microscopic, threadlike nanotubes to communicate with neighboring cells, like a landline phone connection, rather than sending a broadcast signal, researchers at University of Michigan Life Sciences Institute and University of Texas Southwestern Medical Center have discovered.

The findings, which are scheduled for online publication July 1 in Nature, offer new insights on how stem cells retain their identities when they divide to split off a new, specialized cell.

The fruit-fly research also suggests that short-range, cell-to-cell communication may rely on this type of direct connection more than was previously understood, said co-senior author Yukiko Yamashita, a U-M developmental biologist whose lab is located at the Life Sciences Institute.

A July 1, 2015 University of Michigan news release (also on EurekAlert), which originated the news item, expands on the theme,

“There are trillions of cells in the human body, but nowhere near that number of signaling pathways,” she said. “There’s a lot we don’t know about how the right cells get just the right messages to the right recipients at the right time.”

The nanotubes had actually been hiding in plain sight.

The investigation began when a postdoctoral researcher in Yamashita’s lab, Mayu Inaba, approached her mentor with questions about tiny threads of connection she noticed in an image of fruit fly reproductive stem cells, which are also known as germ line cells. The projections linked individual stem cells back to a central hub in the stem cell “niche.” Niches create a supportive environment for stem cells and help direct their activity.

Yamashita, a Howard Hughes Medical Institute investigator, MacArthur Fellow and an associate professor at the U-M Medical School, looked through her old image files and discovered that the connections appeared in numerous images.

“I had seen them, but I wasn’t seeing them,” Yamashita said. “They were like a little piece of dust on an otherwise normal picture. After we presented our findings at meetings, other scientists who work with the same cells would say, ‘We see them now, too.'”

It’s not surprising that the minute structures went overlooked for so long. Each one is about 3 micrometers long; by comparison, a piece of paper is 100 micrometers thick.

While the study looked specifically at reproductive cells in male Drosophila fruit flies, there have been indications of similar structures in other contexts, including mammalian cells, Yamashita said.

Fruit flies are an important model for this type of investigation, she added. If one was to start instead with human cells, one might find something, but the system’s greater complexity would make it far more difficult to tease apart the underlying mechanisms.

The findings shed new light on a key attribute of stem cells: their ability to make new specialized cells while still retaining their identity as stem cells.

Germ line stem cells typically divide asymmetrically. In the male fruit fly, when a stem cell divides, one part stays attached to the hub and remains a stem cell. The other part moves away from the hub and begins differentiation into a fly sperm cell.

Until the discovery of the nanotubes, scientists had been puzzled as to how cellular signals guiding identity could act on one of the cells but not the other, said collaborator Michael Buszczak, an associate professor of molecular biology at UT Southwestern, who shares corresponding authorship of the paper and currently co-mentors Inaba with Yamashita.

The researchers conducted experiments that showed disruption of nanotube formation compromised the ability of the germ line stem cells to renew themselves.

I gather the fruit fly research offers the basis for more extensive investigations into other species and their cell-to-cell communication.

Here’s a link to and a citation for the paper,

Nanotubes mediate niche–stem-cell signalling in the Drosophila testis by Mayu Inaba, Michael Buszczak, & Yukiko M. Yamashita. Nature (2015) doi:10.1038/nature14602 Published online 01 July 2015

This paper is behind a paywall.