Different Facets of Aging in Human Mesenchymal Stem Cells
- 1 August 2010
- journal article
- review article
- Published by Mary Ann Liebert Inc in Tissue Engineering, Part B: Reviews
- Vol. 16 (4), 445-453
- https://doi.org/10.1089/ten.teb.2009.0825
Abstract
Mesenchymal stem cells (MSCs) have to be culture expanded to gain relevant cell numbers for therapeutic applications. However, within 2–3 months the proliferation rate of MSCs decays until they ultimately reach a senescent state. This is accompanied by enlarged morphology, reduced expression of surface markers, and decreased differentiation potential. So far it is only scarcely understood how long-term culture affects MSC preparations, and five processes seem to be involved: (1) MSCs are composed of different sub-populations, and due to different proliferation rates the heterogeneity changes in the course of in vitro expansion; (2) cells in culture acquire mutations and other stochastic cellular defects; (3) self-renewal of MSCs may be impaired under culture conditions, leading to gradual differentiation; (4) the number of cell divisions might be restricted (e.g., by loss of telomeres), and (5) replicative senescence might be associated with the aging process of the organism. There is a growing perception that long-term culture has to be taken into account—especially for clinical applications. On the other hand, the state of replicative senescence is poorly defined by the number of population doublings or even by the number of passages. Reliable molecular measures for cellular aging are urgently needed.Keywords
This publication has 85 references indexed in Scilit:
- Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cellsChromosome Research, 2009
- Senescence impairs successful reprogramming to pluripotent stem cellsGenes & Development, 2009
- Linking the p53 tumour suppressor pathway to somatic cell reprogrammingNature, 2009
- The Ink4/Arf locus is a barrier for iPS cell reprogrammingNature, 2009
- Suppression of induced pluripotent stem cell generation by the p53–p21 pathwayNature, 2009
- Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing mediumBone Marrow Transplantation, 2008
- Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapiesMechanisms of Ageing and Development, 2008
- Human Embryonic Stem Cells: Mechanisms to Escape Replicative Senescence?Stem Cell Reviews, 2007
- Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statementCytotherapy, 2006
- Historical claims and current interpretations of replicative agingNature Biotechnology, 2002