Progress Towards Ways to Make Old Stem Cells More Effective for Heart Repair


Pioneer Founding member

Stem cells in old tissues are less active than stem cells in young tissues, meaning a lesser supply of cells to maintain the tissue, and a consequent slow loss of function. The evidence to date suggest that a sizable part of this decline is a reaction to rising levels of tissue damage and the changing balance of cell signaling that results from that damage. There is certainly damage occurring to stem cells themselves, but that doesn't appear to contribute to as great a degree until very late in life. This means that it is feasible to think about ways to force stem cells to get back to work, to rejuvenate their behavior if not their level of intrinsic damage, and assess the benefits against the potential risks, such as a higher rate of cancer. The stem cell therapies of the past few decades suggest that this cancer risk is lower than was expected, that evolution has left us more wiggle room for therapeutic enhancement of stem cell activity in the old than it might have done.

Ischemic heart disease affects a majority of people, especially elderly patients. Recent studies have utilized autologous adult stem cells and progenitor cells as a treatment option to heal cardiac tissue after myocardial infarction. However, donor cells from aging patients are more likely to be in a senescent stage. Rejuvenation is required to reverse the damage levied by aging and promote a youthful phenotype. This review aims to discuss current strategies that are effective in rejuvenating aging cardiac stem cells and represent novel therapeutic methods to treat the aging heart.

Recent literature mainly focuses on three approaches that aim to reverse cardiac aging: genetic modification, pharmaceutical administration, and optimization of extracellular factors. In vitro genetic modification can be used to overexpress or knock down certain genes and allow for reversal of the aging phenotype. Pharmaceutical administration is another approach that allows for manipulation of signaling pathways related to cell proliferation and cell senescence. Since the stem cell niche can contribute to the age-related decline in stem cell function, rejuvenation strategies also include optimization of extracellular factors.

Overall, improving the intrinsic properties of aging stem cells as well as the surrounding environment allows these cells to adopt a phenotype similar to their younger counterparts. Recent studies show promising results of the ability of these techniques to rejuvenate the aging heart. However, more understanding of the combinatorial effects of these interventions and fine-tuning of these techniques is required to evaluate the translational potential of these methods. Each strategy has its own advantages and disadvantages. The success of myocardial regenerative treatment will require teamwork across various disciplines to make stem cell therapy a reliable method for cardiac repair.