Stem Cell Transplantation for Frailty

Extract

It was reported over 50 years ago that old age is associated with depletion and loss of function of stem cells (1). Since that time, there has been extensive research confirming the deleterious effects of aging on all types of stem cells, and a growing belief that such age-related changes in stem cells further accelerate tissue and organismal aging (2–4). There are two major divisions of stem cells, embryonic stem cells and adult stem cells. Embryonic stem cells are only present at the embryonic state and are pluripotent, giving rise to any fetal or adult cell type. Similarly, inducible pluripotent stem cells have the potential to differentiate into cells of various lineages, and are thus similar to embryonic stem cells. Inducible pluripotent stem cells are derived experimentally from differentiated somatic cells usually involving activation of the “Yamanaka transcription factors” (Oct4, Sox2, Klf4, Myc; “OSKM”) (5). In contrast, adult stem cells, or tissue-specific stem cells, have restricted lineage potential and are present in both the developing and adult organisms. Adult stem cells respond to tissue injury throughout life by proliferation and differentiation, leading to telomere attrition and eventually reduced proliferative capacity. Today, stem cells are considered to play a central role in aging and have been included among the Seven Pillars of Aging (6) and the nine Hallmarks of Aging (7).