Towards Direct Reprogramming of Heart Fibroblasts into Cardiomyocytes
A promising approach to inducing regeneration from injury and age-related fibrosis in the heart is the reprogramming of fibroblast cells into heart muscle cells, cardiomyocytes. Like all such efforts, much of the work lies in establishing the recipe of regulatory signals needed to produce the desired outcome. The research results reported here are an illustrative example, representative of programs taking place in many laboratories, in which scientists are attempting to improve on the discovered forms of reprogramming in order to make them efficient enough to be useful as a basis for regenerative therapies.
Mammalian hearts have almost no ability to grow new heart muscle cells, called cardiomyocytes, after birth. Thus, dead tissue after an adult heart attack is not repaired with new cardiomyocytes. It is instead replaced with scar tissue that weakens the pumping power of the heart and often leads to heart failure. One promising strategy to remuscularize the injured heart is the direct cardiac reprogramming of heart fibroblast cells into cardiomyocytes.
Current cocktails for direct reprogramming of human fibroblasts suffer from low efficiency and insufficient production of functional cardiomyocytes. Researchers have now identified TBX20 as the most underexpressed factor when they compared cardiomyocytes induced from fibroblasts using a current reprogramming cocktail versus functional cardiomyocytes. The addition of TBX20 promoted cardiac reprogramming, as seen in activation of cardiac genes related to sarcomere structure, ion channels and heart contractions. A sarcomere is the smallest functional unit of striated muscle.
Mechanistically, the researchers found that TBX20 was bound to and activated cardiac gene enhancers. In detail, TBX20 primarily activated genes at the late stage of reprogramming, enhancing calcium flux, contractility, and mitochondrial function in the induced-cardiomyocytes. Mitochondria are the energy source for heart muscle contractions. TBX20 appeared to help the mitochondria in the induced cardiomyocytes switch to an adult cardiomyocyte-like respiration.
In the grand scheme of things with regard to effective rejuvenation medicine, what role do you think will cellular reprogramming will play? It seems to me that reprogramming will be needed in the process of replenishing cells, whether that's done outside the body or within the body. (not to belittle work on fibroblasts as well).
I guess technically no one officially knows what Altos is up to(?) But many articles suggest that it's mainly working on reprogramming techniques... so ....best of luck and progress to them. It seems like their category of work will be essential.