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
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?