Are Benefits from Cardiac Stem Cell Therapy Due to an Immune Response to Transplanted Cells?

As this article notes, researchers have recently suggested that the benefits to heart function observed over many years of stem cell therapies are not in fact due to any action of the cells themselves, not even cell signaling mechanisms such as release of exosomes, but are rather due to an immune response to the transplanted cells. The study reported here illustrates the point by showing some degree of regeneration of injured heart tissue to take place in mice when the debris of dead cells is transplanted. We might compare these findings with the body of work showing that delivery of exosomes can spur cardiac regeneration; few portions of the field of stem cell therapy are lacking a good supply of contradictory evidence.

For 15 years, scientists have put various stem cells into seriously ill patients' hearts in hopes of regenerating injured muscle and boosting heart function. A new mouse study may finally debunk the idea behind the controversial procedure, showing the beneficial effects of two types of cell therapy are caused not by the rejuvenating properties of stem cells, but by the body's wound-healing response - which can also be triggered by injecting dead cells or a chemical into the heart.

The discovery will have to be repeated and investigated in human tissue, but the emergence of a likely explanation for how heart cell therapy can have modest benefits comes after years of hype, hope and disagreement about stem cells' potential to heal broken hearts. Experimental therapies have been tested in hundreds of patients with heart disease, even as doubts have grown about the underlying scientific rationale. The idea that the cells could regenerate the heart was intuitively attractive and captured a field searching for therapies to offer desperate patients, and many scientists started companies to try to commercialize different cell types. The new work provides a long-awaited explanation - one that some outside scientists argued does not support more trials with the cells.

Five years ago, researchers debunked the idea that one type of heart stem cell, called a cardiac progenitor cell, was a stem cell at all. Contrary to expectations, those cells were not regenerating appreciable amounts of heart muscle after being injected into injured mouse hearts. Some scientists and physicians, many of whom had built careers on the use of cells as therapy, argued that it wasn't the cells themselves doing the repair but, rather, factors that the cells secreted. In the new study, scientists reported that the modest beneficial effects of injecting either cardiac progenitor cells or bone marrow cells into the injured mouse heart don't appear to be specific to the cell therapy. Modest improvements in heart function, the result of the healing of a heart attack scar, can also be triggered by injecting dead cellular debris or a chemical that stimulates the immune system.

"The progression, after we figured out that was wrong, was that people were hoping the cells we inject make a magic soup ... that revitalize the cells. What we did and showed is there is no magic soup. You're injecting cells, they're dying and stimulating an immune response."

Link: https://www.washingtonpost.com/health/2019/11/27/benefits-stem-cell-heart-therapy-may-have-nothing-do-with-stem-cells-mouse-study-suggests/

Comments

Hmm, delivering cell debris doesn't rule out stem cell signaling

Posted by: Cuberat at December 9th, 2019 7:20 AM

This is an interesting finding

One of the biggest paradoxes in nature is how all of the organisms that undergo the most complex forms of organ and limb regeneration, utilize their innate immune system in a pro-regenerative manner - and some inflammation is very important here

A few links:

https://www.sciencedirect.com/science/article/pii/S1742706117300661

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171206/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092101/

https://www.nature.com/articles/s41536-017-0027-y

Posted by: Ira S. Pastor at December 9th, 2019 12:06 PM

Hi Ira,

Is that why regeneration requires some tgf-b but that in healing often reducing it reduces fibrosis and improves healing?

Posted by: Mark at December 9th, 2019 12:49 PM
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