September 24, 2020

The Niche

Knoepfler lab stem cell blog

Can Hearts Repair Themselves Via Stem Cells: More on Hot Topic

Can hearts repair themselves via stem cell-like mechanisms?

Sometimes what we scientists all know to be true turns out later on to be wrong and there are clear instances of this in the stem cell field.

For example for decades the dogma was that the adult mammalian brain did not have stem cells, but now everyone knows that the adult brain does have stem cells. What we perceive as factual can change over time.

Yamanaka disproved the entrenched notion that differentiated cells were permanently locked into that differentiated state with his revolutionary findings on induced pluripotent stem cells.

Today the cardiac stem cell field finds itself at an interesting crossroads with a hot, controversial question:

Can damaged heart muscle repair itself via stem cells?

heart stem cells

Some say “yes” there are cardiac stem cells and that they can mediate repair. Others feel just as strongly that there are not such cells.

I recently asked cardiac stem cell expert, Deepak Srivastava for his thoughts on this in a previous post and found his answer compelling.

My sense is that the view that there are some heart stem cells, but perhaps not enough to mediate significant repair predominates today. That’s my current view too.

You can see the diversity of papers in PubMed with “Heart Regeneration” or “Cardiac Regeneration” or “Cardiac stem cells” in their titles.

It seems that a lot more people believe that there are a small population of cardiac stem-like cells (perhaps mobilized and/or reprogrammed by injury) than support the bolder notion that these cells can mediate clinically significant endogenous repair of the heart.

One of the biggest advocates of endogenous cardiac stem cells and repair, Piero Anversa of Harvard and Brigham and Women’s Hospital, has become one of the most controversial as well. His papers have come under fire and one has been retracted. Anversa is the subject of a Harvard investigation and is suing Harvard for how it has conducted the investigation and other matters related to his work.

Could his work still be right that hearts can indeed repair themselves? At this time I am very skeptical.

Still there are glimpses of interesting stem cell activity in the mammalian heart.

A November 2014 Cell Stem Cell paper from the lab of Juan Carlos Izpisua Belmonte, entitled “In Vivo Activation of a Conserved MicroRNA Program Induces Mammalian Heart Regeneration”, argues for endogenous mammalian heart regeneration in part via dedifferentiation of cells into stem-like cells. You can take a look at its graphical abstract above.

Even if the endogenous stem cell-like activity in the heart is not enough usually to mediate clinically significant repair, the good news is that by deciphering the molecular basis of this activity the field could still open the door to powerful new treatments for heart disease. For instance, if the heart naturally replaces 1 in 200 cells per year, perhaps cardiac researchers can find a way to boost that by an order of magnitude with a drug and have a meaningful impact for patients.

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