Bone Marrow-Derived Cells: The Influence of Aging and Cellular Senescence
During the course of an entire lifespan, tissue repair and regeneration is made possible by the presence of adult stem cells. Stem cell expansion, maintenance, and differentiation must be tightly controlled to assure longevity. Hematopoietic stem cells (HSC) are greatly solicited given the daily high blood cell turnover. Moreover, several bone marrow-derived cells including HSC, mesenchymal stromal cells (MSC), and endothelial progenitor cells (EPC) also significantly contribute to peripheral tissue repair and regeneration, including tumor formation. Therefore, factors influencing bone marrow-derived cell proliferation and functions are likely to have a broad impact. Aging has been identified as one of these factors. One hypothesis is that aging directly affects stem cells as a consequence of exhaustive proliferation. Alternatively, it is also possible that aging indirectly affects stem cells by acting on their microenvironment. Cellular senescence is believed to have evolved as a tumor suppressor mechanism capable of arresting growth to reduce risk of malignancy. In opposition to apoptosis, senescent cells accumulate in tissues. Recent evidence suggests their accumulation contributes to the phenotype of aging. Senescence can be activated by both telomere-dependent and telomere-independent pathways. Genetic alteration, genome-wide DNA damage, and oxidative stress are inducers of senescence and have recently been identified as occurring in bone marrow-derived cells. Below is a review of the link between cellular senescence, aging, and bone marrow-derived cells, and the possible consequences aging may have on bone marrow trans plantation procedures and emerging marrow-derived cell-based therapies.
KeywordsSenescence Aging Bone marrow-derived cells Oxidative stress Cyclin-dependent kinase inhibitor
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- Cipolleschi MG, D’Ippolito G, Bernabei PA, Caporale R, Nannini R, Mariani M, Fabbiani M, Rossi-Ferrini P, Olivotto M, Dello Sbarba P (1997) Severe hypoxia enhances the formation of erythroid bursts from human cord blood cells and the maintenance of BFU-E in vitro. Exp Hematol 25:1187–1194PubMedGoogle Scholar
- Edelberg JM, Lee SH, Kaur M, Tang L, Feirt NM, McCabe S, Bramwell O, Wong SC, Hong MK (2002) Platelet-derived growth factor-AB limits the extent of myocardial infarction in a rat model: feasibility of restoring impaired angiogenic capacity in the aging heart. Circulation 105:608–613PubMedCrossRefGoogle Scholar
- Piacibello W, Bruno S, Sanavio F, Droetto S, Gunetti M, Ailles L, Santoni de Sio F, Viale A, Gammaitoni L, Lombardo A, Naldini L, Aglietta M (2002) Lentiviral gene transfer and ex vivo expansion of human primitive stem cells capable of primary, secondary, and tertiary multilineage repopulation in NOD/SCID mice. Nonobese diabetic/severe combined immunodeficient. Blood 100:4391–4400PubMedCrossRefGoogle Scholar