Delivering a Synthetic Stem Cell Niche Alongside Transplanted Stem Cells Can Improve the Therapy

Stem cells reside within a stem cell niche, a supporting environment that provides stem cells with the conditions they need. The lack of this niche is why most transplanted stem cells survive only a short time. Many of the potential incremental improvements to stem cell transplants under development work because they incorporate some of the functions of the niche into the therapy, usually by delivering specific signals or nutrients for a period of time. This is an example of the type:

Although stem cells have shown enormous promise in repairing organs after injury, using them in the heart itself has not yielded the expected results because very few of the transplanted cells survive in the heart. When the heart beats, it pushes cells injected into the heart wall out into the lungs before they get a chance to attach to the wall. Additionally, when stem cells move from the culture flasks they are grown in and into a solution for injection in the heart, their metabolism slows, causing them to die in several hours unless they are given the opportunity to attach to tissue. Researchers have tried to improve stem cell retention in the heart by injecting millions, only to have a mere 10-to-20 percent stick around an hour after injection. And even then a large number of these cells die within 24 hours due to a sluggish metabolism. "If we could inject fewer cells soon after heart attacks and coax them to proliferate following transplantation, we could limit scar formation and be more successful with re-growing new heart muscle."

The researchers developed a hydrogel that combines serum, a protein-filled component of blood that contains everything cells need to survive, with hyaluronic acid, a molecule already present in the heart and in the matrix that surrounds and supports cells. By mixing these two components, the researchers created a sticky gel that functioned as a synthetic stem cell niche: It encapsulated stem cells while nurturing them and rapidly restored their metabolism. Tests in petri dishes showed that both adult and embryonic stem cells encapsulated in this material not only survived at levels near 100 percent but thrived for days and proliferated. The encapsulated cells also showed markedly higher production of growth factors known to be involved in cardiac repair compared with stem cells that weren't encapsulated in the gel.

When the cell-gel combination was injected into living rat hearts, about 73 percent of the cells were retained in the hearts after an hour, compared with 12 percent of cells suspended in a solution. Over the next seven days, the number of regular solution-based transplanted cells continued to decline, whereas cells within the hydrogel increased in number. In rat models of heart attack damage, moreover, the team reports that the hydrogel with encapsulated cells improved pumping efficiency of the left ventricle over the four weeks after injection by 15 percent, compared with 8 percent from cells in solution. Even injections of the hydrogel on its own significantly improved heart function and increased the number of blood vessels in the region of the heart attack.



This seems like an excellent solution to at least some of the signaling environment issues, although it seems to be better for specific areas of gross physical damage.

Posted by: Slicer at September 25th, 2015 10:36 AM

So this research suggests that the previous medical tourism stem cell treatments for heart disease were baloney then?

Posted by: Jim at September 25th, 2015 12:56 PM

@Jim: They weren't as effective as hoped overall, but certainly produced measurable benefits for many people. "Not as good as they could be now," would be a better way of putting it.

Posted by: Reason at September 25th, 2015 3:47 PM

This is a big step towards regenerative medicine and is something I am investigating for testing. Very positive news indeed for artificial niche and a possible alternative to telomerase induction too.

Posted by: Steve h at September 26th, 2015 10:30 AM

Big step foward? The pumping efficiency went from 8% to 15%. Sounds pretty meaningless to me.

Posted by: jim at September 28th, 2015 1:39 AM

Not at all Jim its the beginning of improved stem cell therapy. That is only going to get better.

Posted by: Steve h at September 28th, 2015 2:22 PM

This is also after only four weeks of therapy. Repeat infusion and more time could potentially improve further on this. Couple this with the improved quality procedure that cnio has developed and the improvement could rise further. It may seem a small number but the potential is greater.

Posted by: Steve h at September 29th, 2015 1:21 AM

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