Current Progress in the Rejuvenation of Aging Stem/Progenitor Cells for Improving the Therapeutic Effectiveness of Myocardial Repair

Abstract

Ischemic heart disease affects a majority of people, especially elderly patients. Recent studies have utilized autologous adult stem/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.

Introductory Chapter: Aging is a Preventable Disorder

“…The cumulative effects of the years cause to overall deterioration of the body. As an accumulated result of various diseases in old age, the functional impairment cause to decrease of capabilty one's own needs [3][4][5][6][7]. A humorist writer defined aging as "hardening of soft tissues and softening of hard tissues in human body" [8].…”

“…A humorist writer defined aging as "hardening of soft tissues and softening of hard tissues in human body" [8]. The mechanism of aging generally expresses with the molecular and cellular damages [4][5][6][7]. Free radical accumulation in mitochondria in consequence of oxidative stress finally results on dysfunctional senescent cells [6].…”

AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells

“…Failure of mitophagy, the autophagy of mitochondria, causes a surge in ROS generation and ROS-mediated injuries [18,19]. Activation of the sirtuins family of NAD + -dependent deacetylases can boost mitophagy and antioxidant mechanisms in cells [20,21]. Increased intracellular NAD + to NADH ratio activates the sirtuin1 (SIRT1) and, in turn, raises the AMPK activity.…”

Rejuvenation of mesenchymal stem cells by extracellular vesicles inhibits the elevation of reactive oxygen species

“…The main principle of pharmacological manipulation is targeting the specific pathways involved in the aging process, such as the mTOR/PI3K, Wnt/β-catenin, and STAT3/NFκB pathways 15 . Genetic intervention includes reversing DNA damage, telomerase reactivation, epigenetic regulation (e.g.…”

“…repair of DNA methylation and histone modification), all conventional approaches that have proven effective for improving the function of several types of stem cells, such as muscle, cardiac, and hematopoietic stem cells 16 . However, both pharmacological and genetic manipulation have limited efficacy, as they can only improve a few specific functions, thus requiring the manipulation of a combination of genes or pathways for a comprehensive approach to rejuvenating stem cells 15,16 .…”