Mining Stem Cell Exomes for Means to Spur Tissue Repair

Researchers are digging into various ways in which stem cells signal other cells to change their behavior, as this this one of the means by which stem cell therapies produce benefits. Identifying the important signalsn would mean that at least some forms of stem cell transplant could be replaced with delivery of the signal molecules instead, probably an easier and cheaper approach to treatment:

The heart, for all its metronomic dependability, has little ability for self-repair. When heart muscle is damaged in a heart attack, the organ cannot replace the dead tissue and grow new. Instead, it must compensate for its lost pumping ability. That compensation comes with a high price: the heart grows large and flabby, and heart contraction weakens. From the start, heart damage seemed a problem custom-made for the burgeoning field of stem cell therapy. As knowledge about stem cells grew, several scientific teams conducted clinical trials on human heart attack victims, injecting damaged hearts with stem cells hoping the cells would take root and make new heart muscle. But results were disappointing.

A little more than a decade ago, researchers discovered that all cells secrete tiny communications modules jammed with an entire work crew of messages for other cells. Researchers renamed these vesicles exosomes. In the current study, researchers used a mouse model of myocardial infarction - heart attack. After infarct, mice received exosomes from either embryonic stem cells or exosomes from another type of cell called a fibroblast; mice receiving the fibroblast exosome served as the control group. The results were unmistakable. Mice that received exosomes from embryonic stem cells showed improved heart function after a heart attack compared to the control group. More heart muscle cells survived after infarct, and the heart exhibited less scar tissue. Fewer heart cells committed suicide - a process known as programmed cell death, or apoptosis. There was greater capillary development around the area of injury in the stem cell exosome group, which improved circulation and oxygen supply to the heart muscle. Further, there was a marked increase in cardiac progenitor cells - that is, the heart's own stem cells - and these survived and created new heart cells. The heartbeat was more powerful in the experimental group compared to the control group, and the kind of unhealthy enlargement that compensates for tissue damage was minimized.

The researchers then tested the effect of one of the most abundant gene-regulating molecules, or microRNAs, found in the stem cell exosome called miR-294. When miR-294 alone was introduced to cardiac stem cells in the laboratory, it mimicked many of the effects seen when the entire exosome was delivered. "To a large extent, this micro-RNA alone can recapitulate the activity of the exosome."



Delivering a small molecule would be messing about with metabolism and similar to the work the CNIO under Maria Blasco did on heart tissue in mice induced to have a heart attack. She used Telomerase to repair the scarring in her case.

Could a combination of transient gene therapy and Stem cells be the answer to repairing the heart?

Posted by: Steve H at June 19th, 2015 7:05 AM

I wonder if exosomes/microRNAs might be the factors that produce the positive results from heterochronic parabiosis, in place of circulating proteins?

It would be nice to have an age-matched map (young vs. old) of some of these microRNAs.

Posted by: Gary at June 19th, 2015 10:18 AM

@Steve H - From a SENS point of view it would be better not to have the infraction in the first place.

What are the (proposed) causes of the infraction... oxidized LDL (intra-cellular junk) leading to blood clots, cross linked ECM in the blood vessel walls, loss of stem cell function (senescent cells, perhaps mitochondrial hot spot reduction), and perhaps just plain cell loss.

Exosomes are only addressing the last type of damage, and they are doing it after the infraction, and they are fighting against the other types of damage that are inhibiting the adult progenitor cells anyway (so probably won't be that effective).

Posted by: Jim at June 19th, 2015 6:36 PM

Good talk from Linda Marban of Capricor at the Rejuvenation Biotechnology conference 2014 with some talk about using exosomes to treat heart diesase post heart attack at the end:

Posted by: Jim at June 20th, 2015 10:32 PM
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