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Effects of the Local Organ and Systemic Environments on Stem Cell Aging

出版	University of California, Berkeley with the University of California, San Francisco, 2008
URL	http://books.google.com.hk/books?id=SKFNAQAAMAAJ&hl=&source=gbs_api

註釋This work uncovers mechanisms of aging within stem cell niches that are evolutionarily conserved between mice and humans, and affect both embryonic and adult stem cells. Specifically, the effects of aged muscle and systemic niches on key molecular identifiers of regenerative potential of human embryonic stem cells (hESCs) and postnatal muscle stem cells (satellite cells) were examined. Results reveal that aged differentiated niches dominantly inhibit the expression of Oct4 in hESC and Myf-5 in activated satellite cells, and reduce proliferation and myogenic differentiation of both embryonic and tissue specific adult stem cells (ASCs). Therefore, the ability of hESCs, and the more differentiated myogenic ASCs to contribute to tissue repair in the old will be restricted, due to the conserved inhibitory influence of aged differentiated niches. Additionally, this work establishes that hESC-derived factors enhance the regenerative potential of both young and importantly, aged muscle stem cells in vitro and in vivo; thus, suggesting that the regenerative outcome of stem cell-based replacement therapies will be determined by a balance between negative influences of aged tissues on transplanted cells and positive effects of embryonic cells on the endogenous regenerative capacity.