Turning Back the Clock to Repair Hearts

The human heart plays an important role in pumping blood to provide oxygen and nutrients to the body. However, it does not contain any heart precursor cells, and most heart cells do not divide, which limits its potential to grow new cells. While the benefit of this lies in preventing heart cancer formation, the resulting drawback is that the heart cannot regenerate and repair tissue damage. As a result, therapies directed at replacing or generating new heart cells to restore heart function, especially after heart injuries, are in high demand but currently lacking.

Researchers at the Max Planck Institute recently developed a solution to this problem using an approach called partial reprogramming in mice. The scientists used four factors, called the Yamanaka factors, that are known to reverse the state of an aged cell back into its original stem cell state. By turning back the clock on cellular aging, these reprogrammed stem cells can then divide and form new cells. A controlled short-term treatment with these factors ensures that these rejuvenated cells do not completely erase their identity, but still retain the information needed to re-develop back into heart cells. Transiently administering this therapy after a heart attack in mice induced partial regeneration of the heart, reduced scarring, and recovered ventricle function.

The ability to use Yamanaka factors to force heart cells to re-enter the cell cycle, divide, and form new heart cells in mice is an important advancement. However, the importance of the dosage and duration of the therapy presents a key challenge. Long-term treatments caused the cells to reach an irreversible newborn-like state that cannot sustain heart function or form abnormal tissue masses. While this tight control may be difficult to translate as a therapy to humans, the finding that the adult tissues’ ability to regenerate can be reactivated has exciting implications for regenerative medicine and raises questions about the potential to perform similar regenerations in other adult tissues.

Yanpu Chen is a scientist in the lab of Johnny Kim at the Max Planck Institute for Heart and Lung Research in Germany.

Managing Correspondent: Lauren Davancaze

Press Articles: “Reversing aging for heart repair,” Science

Original Journal Article: “Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice,” Science

Image Credit: Science Repository

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