Tag Archives: stem cells

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.

Nano and stem cell differentiation at Rutgers University (US)

A Nov. 14, 2014 news item on Azonano features a nanoparticle-based platform for differentiating stem cells,

Rutgers University Chemistry Associate Professor Ki-Bum Lee has developed patent-pending technology that may overcome one of the critical barriers to harnessing the full therapeutic potential of stem cells.

A Nov. 1, 2104 Rutgers University news release, which originated the news item, describes the challenge in more detail,

One of the major challenges facing researchers interested in regenerating cells and growing new tissue to treat debilitating injuries and diseases such as Parkinson’s disease, heart disease, and spinal cord trauma, is creating an easy, effective, and non-toxic methodology to control differentiation into specific cell lineages. Lee and colleagues at Rutgers and Kyoto University in Japan have invented a platform they call NanoScript, an important breakthrough for researchers in the area of gene expression. Gene expression is the way information encoded in a gene is used to direct the assembly of a protein molecule, which is integral to the process of tissue development through stem cell therapeutics.

Stem cells hold great promise for a wide range of medical therapeutics as they have the ability to grow tissue throughout the body. In many tissues, stem cells have an almost limitless ability to divide and replenish other cells, serving as an internal repair system.

Transcription factor (TF) proteins are master regulators of gene expression. TF proteins play a pivotal role in regulating stem cell differentiation. Although some have tried to make synthetic molecules that perform the functions of natural transcription factors, NanoScript is the first nanomaterial TF protein that can interact with endogenous DNA. …

“Our motivation was to develop a highly robust, efficient nanoparticle-based platform that can regulate gene expression and eventually stem cell differentiation,” said Lee, who leads a Rutgers research group primarily focused on developing and integrating nanotechnology with chemical biology to modulate signaling pathways in cancer and stem cells. “Because NanoScript is a functional replica of TF proteins and a tunable gene-regulating platform, it has great potential to do exactly that. The field of stem cell biology now has another platform to regulate differentiation while the field of nanotechnology has demonstrated for the first time that we can regulate gene expression at the transcriptional level.”

Here’s an image illustrating NanoScript and gold nanoparticles,

Courtesy Rutgers University

Courtesy Rutgers University

The news release goes on to describe the platform’s use of gold nanoparticles,

NanoScript was constructed by tethering functional peptides and small molecules called synthetic transcription factors, which mimic the individual TF domains, onto gold nanoparticles.

“NanoScript localizes within the nucleus and initiates transcription of a reporter plasmid by up to 30-fold,” said Sahishnu Patel, Rutgers Chemistry graduate student and co-author of the ACS Nano publication. “NanoScript can effectively transcribe targeted genes on endogenous DNA in a nonviral manner.”

Lee said the next step for his research is to study what happens to the gold nanoparticles after NanoScript is utilized, to ensure no toxic effects arise, and to ensure the effectiveness of NanoScript over long periods of time.

“Due to the unique tunable properties of NanoScript, we are highly confident this platform not only will serve as a desirable alternative to conventional gene-regulating methods,” Lee said, “but also has direct employment for applications involving gene manipulation such as stem cell differentiation, cancer therapy, and cellular reprogramming. Our research will continue to evaluate the long-term implications for the technology.”

Lee, originally from South Korea, joined the Rutgers faculty in 2008 and has earned many honors including the NIH Director’s New Innovator Award. Lee received his Ph.D. in Chemistry from Northwestern University where he studied with Professor Chad. A. Mirkin, a pioneer in the coupling of nanotechnology and biomolecules. Lee completed his postdoctoral training at The Scripps Research Institute with Professor Peter G. Schultz. Lee has served as a Visiting Scholar at both Princeton University and UCLA Medical School.

The primary interest of Lee’s group is to develop and integrate nanotechnologies and chemical functional genomics to modulate signaling pathways in mammalian cells towards specific cell lineages or behaviors. He has published more than 50 articles and filed for 17 corresponding patents.

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

NanoScript: A Nanoparticle-Based Artificial Transcription Factor for Effective Gene Regulation by Sahishnu Patel, Dongju Jung, Perry T. Yin, Peter Carlton, Makoto Yamamoto, Toshikazu Bando, Hiroshi Sugiyama, and Ki-Bum Lee. ACS Nano, 2014, 8 (9), pp 8959–8967 DOI: 10.1021/nn501589f Publication Date (Web): August 18, 2014
Copyright © 2014 American Chemical Society

This paper is behind a paywall.

Wonders of curcumin: wound healing; wonders of aromatic-turmerone: stem cells

Both curcumin and turmerone are constituents of turmeric which has been long lauded for its healing properties. Michael Berger has written a Nanowerk Spotlight article featuring curcumin and some recent work on burn wound healing. Meanwhile, a ScienceDaily news item details information about a team of researchers focused on tumerone as a means for regenerating brain stem cells.

Curcumin and burn wounds

In a Sept. 22, 2014 Nanowerk Spotlight article Michael Berger sums up the curcumin research effort (referencing some of this previous articles on the topic) in light of a new research paper about burn wound healing (Note: Links have been removed),

Despite significant progress in medical treatments of severe burn wounds, infection and subsequent sepsis persist as frequent causes of morbidity and mortality for burn victims. This is due not only to the extensive compromise of the protective barrier against microbial invasion, but also as a result of growing pathogen resistance to therapeutic options.

… Dr Adam Friedman, Assistant Professor of Dermatology and Director of Dermatologic research at the Montefiore-Albert Einstein College of Medicine, tells Nanowerk. “For me, this gap fuels innovation, serving as the inspiration for my research with broad-spectrum, multi-mechanistic antimicrobial nanomaterials.”

In new work, Friedman and a team of researchers from Albert Einstein College of Medicine and Oregon State University have explored the use of curcumin nanoparticles for the treatment of infected burn wounds, an application that resulted in reduced bacterial load and enhancing wound healing.

It certainly seems promising as per the article abstract,

Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent by Aimee E. Krausz, Brandon L. Adler, Vitor Cabral, Mahantesh Navati, Jessica Doerner, Rabab Charafeddine, Dinesh Chandra, Hongying Liang, Leslie Gunther, Alicea Clendaniel, Stacey Harper, Joel M. Friedman, Joshua D. Nosanchuk, & Adam J. Friedman. Nanomedicine: Nanotechnology, Biology and Medicine (article in press) published online 19 September 2014.http://www.nanomedjournal.com/article/S1549-9634%2814%2900527-9/abstract Uncorrected Proof

Burn wounds are often complicated by bacterial infection, contributing to morbidity and mortality. Agents commonly used to treat burn wound infection are limited by toxicity, incomplete microbial coverage, inadequate penetration, and rising resistance. Curcumin is a naturally derived substance with innate antimicrobial and wound healing properties. Acting by multiple mechanisms, curcumin is less likely than current antibiotics to select for resistant bacteria.

Curcumin’s poor aqueous solubility and rapid degradation profile hinder usage; nanoparticle encapsulation overcomes this pitfall and enables extended topical delivery of curcumin.

In this study, we synthesized and characterized curcumin nanoparticles (curc-np), which inhibited in vitro growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in dose-dependent fashion, and inhibited MRSA growth and enhanced wound healing in an in vivo murine wound model. Curc-np may represent a novel topical antimicrobial and wound healing adjuvant for infected burn wounds and other cutaneous injuries.

Two things: This paper is behind a paywall and note the use of the term ‘in vivo’ which means they have tested on animals such as rats and mice for example, but not humans. Nonetheless, it seems a promising avenue for further exploration.

Interestingly, there was an attempt in 1995 to patent turmeric for use in wound healing as per my Dec. 26, 2011 posting which featured then current research on turmeric,

There has already been one court case regarding a curcumin patent,

Recently, turmeric came into the global limelight when the controversial patent “Use of Turmeric in Wound Healing” was awarded, in 1995, to the University of Mississippi Medical Center, USA. Indian Council of Scientific and Industrial Research (CSIR) aggressively contested this award of the patent. It was argued by them that turmeric has been an integral part of the traditional Indian medicinal system over several centuries, and therefore, is deemed to be ‘prior art’, hence is in the public domain. Subsequently, after protracted technical/legal battle USPTO decreed that turmeric is an Indian discovery and revoked the patent.

One last bit about curcumin, my April 22, 2014 posting featured work in Iran using curcumin for cancer-healing.

Tumerone

This excerpt from a Sept. 25, 2014, news item in ScienceDaily represents the first time that tumerone has been mentioned here,

A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published today in the open access journal Stem Cell Research & Therapy. The findings suggest aromatic turmerone could be a future drug candidate for treating neurological disorders, such as stroke and Alzheimer’s disease.

A Sept. 25, 2014 news release on EurekAlert provides more information,

The study looked at the effects of aromatic (ar-) turmerone on endogenous neutral stem cells (NSC), which are stem cells found within adult brains. NSC differentiate into neurons, and play an important role in self-repair and recovery of brain function in neurodegenerative diseases. Previous studies of ar-turmerone have shown that the compound can block activation of microglia cells. When activated, these cells cause neuroinflammation, which is associated with different neurological disorders. However, ar-turmerone’s impact on the brain’s capacity to self-repair was unknown.

Researchers from the Institute of Neuroscience and Medicine in Jülich, Germany, studied the effects of ar-turmerone on NSC proliferation and differentiation both in vitro and in vivo. Rat fetal NSC were cultured and grown in six different concentrations of ar-turmerone over a 72 hour period. At certain concentrations, ar-turmerone was shown to increase NSC proliferation by up to 80%, without having any impact on cell death. The cell differentiation process also accelerated in ar-turmerone-treated cells compared to untreated control cells.

To test the effects of ar-turmerone on NSC in vivo, the researchers injected adult rats with ar-turmerone. Using PET imaging and a tracer to detect proliferating cells, they found that the subventricular zone (SVZ) was wider, and the hippocampus expanded, in the brains of rats injected with ar-turmerone than in control animals. The SVZ and hippocampus are the two sites in adult mammalian brains where neurogenesis, the growth of neurons, is known to occur.

Lead author of the study, Adele Rueger, said: “While several substances have been described to promote stem cell proliferation in the brain, fewer drugs additionally promote the differentiation of stem cells into neurons, which constitutes a major goal in regenerative medicine. Our findings on aromatic turmerone take us one step closer to achieving this goal.”

Ar-turmerone is the lesser-studied of two major bioactive compounds found in turmeric. The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties

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

Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo by Joerg Hucklenbroich, Rebecca Klein, Bernd Neumaier, Rudolf Graf, Gereon Rudolf Fink, Michael Schroeter, and Maria Adele Rueger. Stem Cell Research & Therapy 2014, 5:100  doi:10.1186/scrt500

This is an open access paper.

Targeted nanoparticles stimulate growth of healthy heart cells in damaged hearts

Don’t get too excited, the research is at the rat stage sometimes called ‘animal models’ as in ‘these nanoparticles are being tested on animal models’. Still it’s exciting news from North Carolina State University (NCSU; my second item from that university today, Sept. 12, 2014).

From a Sept. 12, 2014 news item on Azonano,

A targeted nanoparticle created by researchers at North Carolina State University and the Cedars-Sinai Heart Institute may help heart attack patients regenerate healthy heart tissue without using donated or processed stem cells. This new nanomedicine could also alleviate some of the difficulties involved with stem cell therapy, including treatment delays and invasive procedures.

A Sept. ?, 2014 NCSU news release, which originated the news item, provides a little more detail about the work,

The particle, a “magnetic bi-functional cell engager” called MagBICE, consists of an iron platform with two different antibodies attached. These antibodies have different functions – one locates a patient’s own stem cells after a heart attack, and the other grabs injured tissue, allowing MagBICE to act as a matchmaker between injury and repair crew. The iron platform makes MagBICE magnetically active, allowing physicians to direct the particles to the heart with an external magnetic field. The iron platform also enables magnetic resonance imaging (MRI).

Ke Cheng, associate professor of regenerative medicine at NC State, and his colleagues at Cedars-Sinai Heart Institute tested MagBICE in rats and found that the particle was effective in redirecting stem cells in the blood to the injured heart. [emphasis] Additionally, MagBICE was easier and faster to administer than current stem cell therapy products.

“MagBICE optimizes and amplifies the body’s own repair process, which means we don’t have to worry about patient rejection of donated stem cells, or delay treatment while a patient’s stem cells are being processed, purified and prepared,” Cheng says. “The drug can be offered to patients immediately after blood vessels to the damaged areas are reopened and can be given intravenously, which isn’t possible with stem cell therapy.”

Courtesy of NCSU, there’s an artist’s illustration of the MagBICE and the heart,

MagBICE engaging therapeutic stem cells with injured cardiomyocytes. Credit: Alice Harvey, NC State

MagBICE engaging therapeutic stem cells with injured cardiomyocytes. Credit: Alice Harvey, NC State

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

Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting by Ke Cheng, Deliang Shen, M. Taylor Hensley, Ryan Middleton, Baiming Sun, Weixin Liu, Geoffrey De Couto, & Eduardo Marbán. Nature Communications 5, Article number: 4880 doi:10.1038/ncomms5880 Published 10 September 2014

This is an open access paper.

Growing new brain cells for implants

The dream is that one day this research will allow doctors to replace damaged or destroyed brain cells. According to the May 7, 2013 news release on EurekAlert,

A key type of human brain cell developed in the laboratory grows seamlessly when transplanted into the brains of mice, UC [University of California] San Francisco researchers have discovered, raising hope that these cells might one day be used to treat people with Parkinson’s disease, epilepsy, and possibly even Alzheimer’s disease, as well as and complications of spinal cord injury such as chronic pain and spasticity.

“We think this one type of cell may be useful in treating several types of neurodevelopmental and neurodegenerative disorders in a targeted way,” said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF [University of California San Francisco] and co-lead author on the paper.

The May 7, 2013 University of California San Francisco news release by Jeffrey Norris, which originated the release on EurekAlert, provides more detail about the work,

The researchers generated and transplanted a type of human nerve-cell progenitor called the medial ganglionic eminence (MGE) cell, in experiments described in the May 2 edition of Cell Stem Cell. Development of these human MGE cells within the mouse brain mimics what occurs in human development, they said.

To generate MGE cells in the lab, the researchers reliably directed the differentiation of human pluripotent stem cells — either human embryonic stem cells or induced pluripotent stem cells derived from human skin. These two kinds of stem cells have virtually unlimited potential to become any human cell type. When transplanted into a strain of mice that does not reject human tissue, the human MGE-like cells survived within the rodent forebrain, integrated into the brain by forming connections with rodent nerve cells, and matured into specialized subtypes of interneurons

The researchers are investigating applications other than brain cell replacement or repair (from the UCSF news release),

Previously, UCSF researchers led by Allan Basbaum, PhD, chair of anatomy at UCSF, have used mouse MGE cell transplantation into the mouse spinal cord to reduce neuropathic pain, a surprising application outside the brain. Kriegstein, Nicholas and colleagues now are exploring the use of human MGE cells in mouse models of neuropathic pain and spasticity, Parkinson’s disease and epilepsy.

“The hope is that we can deliver these cells to various places within the nervous system that have been overactive and that they will functionally integrate and provide regulated inhibition,” Nicholas said.

The researchers also plan to develop MGE cells from induced pluripotent stem cells derived from skin cells of individuals with autism, epilepsy, schizophrenia and Alzheimer’s disease, in order to investigate how the development and function of interneurons might become abnormal — creating a lab-dish model of disease.

There is at least one hurdle to be overcome (from the UCSF news release),

One mystery and challenge to both the clinical and pre-clinical study of human MGE cells is that they develop at a slower, human pace, reflecting an “intrinsic clock”. In fast-developing mice, the human MGE-like cells still took seven to nine months to form interneuron subtypes that normally are present near birth.

“If we could accelerate the clock in human cells, then that would be very encouraging for various applications,” Kriegstein said.

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

Functional Maturation of hPSC-Derived Forebrain Interneurons Requires an Extended Timeline and Mimics Human Neural Development by Cory R. Nicholas, Jiadong Chen, Yunshuo Tang, Derek G. Southwell, Nadine Chalmers, Daniel Vogt, Christine M. Arnold, Ying-Jiun J. Chen, Edouard G. Stanley, Andrew G. Elefanty, Yoshiki Sasai, Arturo Alvarez-Buylla, John L.R. Rubenstein, Arnold R. Kriegstein. Cell Stem Cell, Volume 12, Issue 5, 573-586, 2 May 2013

Copyright © 2013 Elsevier Inc. All rights reserved.
10.1016/j.stem.2013.04.005

This research put in me in mind of my Mar. 15, 2013 posting titled, Growing a tooth—as an adult, when I featured research at King’s College London where scientists had successfully used mouse stem cells to  grow teeth in adult mice. The researchers hope to one day be able to do the same in humans.

If vat-grown burgers are here, what are the social implications?

The Jan. 17, 2013 news item on Nanowerk about Dr. Neil Stephens and his research into the social implications of vat-grown (aka, in vitro meat) poses some interesting questions,

he [sic] world’s first laboratory-grown hamburger has been produced by Professor Mark Post and his team in Maastricht, representing something radically new in our world. Dr Neil Stephens, Research Associate at Cesagen (Cardiff School of Social Sciences), has been researching the social and ethical issues of this technology and what this innovation in stem cell science might mean for us in 2013.

Will we be eating burgers made in test-tubes in the near future? That is probably unlikely considering Professor Post’s burger costs around £200,000 to produce.

The University of Cardiff Jan. 16, 2013 news release,which originated the news item, goes on to explain why Stephens is conducting this investigation,

However, the benefits this new technology can deliver – according to the scientists – include slaughter-free meat that is healthier and free from animal to human disease. The meat could also be grown during space travel and could have a much smaller environmental impact than today’s whole-animal reared meat. But it is not yet clear if any of these can be delivered in a marketable form.

Since 2008, Dr Stephens has been investigating these ‘social promises’ by interviewing most of the scientists across the world who are involved in this project. He looks to understand how this community of scientists came together and what strategies they use to justify the promises they make.

Professor Mark Post’s work at the University of Maastricht (Holland) was covered extensively last year when it was presented at the 2012 AAAS (American Ass0ciation for the Advancement of Science) meeting in Vancouver. This Feb. 19, 2012 article by Pallab Ghosh for BBC (British Broadcasting Corporation) online highlights some of the discussion which took place then,

Dutch scientists have used stem cells to create strips of muscle tissue with the aim of producing the first lab-grown hamburger later this year.

The aim of the research is to develop a more efficient way of producing meat than rearing animals.

Professor Post’s group at Maastricht University in the Netherlands has grown small pieces of muscle about 2cm long, 1cm wide and about a mm thick.

They are off-white and resemble strips of calamari in appearance. These strips will be mixed with blood and artificially grown fat to produce a hamburger by the autumn [2012].

…Some estimate that food production will have to double within the next 50 years to meet the requirements of a growing population. During this period, climate change, water shortages and greater urbanisation will make it more difficult to produce food.

Prof Sean Smukler from the University of British Columbia said keeping pace with demand for meat from Asia and Africa will be particularly hard as demand from these regions will shoot up as living standards rise. He thinks that lab grown meat could be a good solution.

But David Steele, who is president of Earthsave Canada, said that the same benefits could be achieved if people ate less meat.

“While I do think that there are definite environmental and animal welfare advantages of this high-tech approach over factory farming, especially, it is pretty clear to me that plant-based alternatives… have substantial environmental and probably animal welfare advantages over synthetic meat,” he said.

Dr Steele, who is also a molecular biologist, said he was also concerned that unhealthily high levels of antibiotics and antifungal chemicals would be needed to stop the synthetic meat from rotting.

There doesn’t seem to be any more recent news about vat-grown meat from Post’s team at the University of Maastricht; the interest in Stephens’ sociological work on the topic seems to have been stimulated by his inclusion in the UK’s Economic and Social Research Council’s (ESRC) annual publication, (Britain in magazine) Britain in 2013.

Here’s more about Stephens’ and his sociological inquiry,

Squishy knees and tissue engineering at Johns Hopkins

Researchers at Johns Hopkins University School of Medicine’s Translational Tissue Engineering Center (TTEC) have developed a material (a kind of hydrogel) which they use with a new technique they’ve developed for growing new tissue and cartilage in knees. From the Jan. 15, 2013 news release on EurekAlert,

Proof-of-concept clinical trial in 18 patients shows improved tissue growth

In a small study, researchers reported increased healthy tissue growth after surgical repair of damaged cartilage if they put a “hydrogel” scaffolding into the wound to support and nourish the healing process. The squishy hydrogel material was implanted in 15 patients during standard microfracture surgery, in which tiny holes are punched in a bone near the injured cartilage. The holes stimulate patients’ own specialized stem cells to emerge from bone marrow and grow new cartilage atop the bone.

“Our pilot study indicates that the new implant works as well in patients as it does in the lab, so we hope it will become a routine part of care and improve healing,” says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Johns Hopkins University School of Medicine’s Translational Tissue Engineering Center (TTEC). Damage to cartilage, the tough-yet-flexible material that gives shape to ears and noses and lines the surface of joints so they can move easily, can be caused by injury, disease or faulty genes. Microfracture is a standard of care for cartilage repair, but for holes in cartilage caused by injury, it often either fails to stimulate new cartilage growth or grows cartilage that is less hardy than the original tissue.

Here are more details from the Johns Hopkins Jan. 15, 2013 news release,

Tissue engineering researchers, including Elisseeff, theorized that the specialized stem cells needed a nourishing scaffold on which to grow, but demonstrating the clinical value of hydrogels has “taken a lot of time,” Elisseeff says. By experimenting with various materials, her group eventually developed a promising hydrogel, and then an adhesive that could bind it to the bone.

After testing the combination for several years in the lab and in goats, with promising results, she says, the group and their surgeon collaborators conducted their first clinical study, in which 15 patients with holes in the cartilage of their knees received a hydrogel and adhesive implant along with microfracture. For comparative purposes, another three patients were treated with microfracture alone. After six months, the researchers reported that the implants had caused no major problems, and MRIs showed that patients with implants had new cartilage filling an average 86 percent of the defect in their knees, while patients with only microfracture had an average of 64 percent of the tissue replaced. Patients with the implant also reported a greater decrease in knee pain in the six months following surgery, according to the investigators.

The trial continues, has enrolled more patients and is now being managed by a company called Biomet. The trial is part of efforts to win European regulatory approval for the device.

In the meantime, Elisseeff says her team has begun developing a next-generation implant, one in which the hydrogel and adhesive will be combined in a single material. In addition, they are working on technologies to lubricate joints and reduce inflammation.

The study has been published in the AAAS’s (American Association for the Advancement of Science) Science Translational Medicine journal,

Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite

Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel

Sci Transl Med 9 January 2013:
Vol. 5 no. 167 pp. 167ra6DOI:10.1126/scitranslmed.3004838

This article is behind a paywall and for some reason the authors are listed only in the news release,

Jennifer Elisseeff, Blanka Sharma, Sara Fermanian, Matthew Gibson, Shimon Unterman, Daniel A. Herzka, Jeannine Coburn and Alexander Y. Hui of the Johns Hopkins School of Medicine; Brett Cascio of Lake Charles Memorial Hospital; Norman Marcus, a private practice orthopedic surgeon; and Garry E. Gold of Stanford University