Reduced Reactivation from Dormancy but Maintained Lineage Choice of Human Mesenchymal Stem Cells with Donor Age
Open Access
- 5 August 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (8), e22980
- https://doi.org/10.1371/journal.pone.0022980
Abstract
UNLABELLED: Mesenchymal stem cells (MSC) are promising for cell-based regeneration therapies but up to date it is still controversial whether their function is maintained throughout ageing. Aim of this study was to address whether frequency, activation in vitro, replicative function, and in vitro lineage choice of MSC is maintained throughout ageing to answer the question whether MSC-based regeneration strategies should be restricted to younger individuals. MSC from bone marrow aspirates of 28 donors (5-80 years) were characterized regarding colony-forming unit-fibroblast (CFU-F) numbers, single cell cloning efficiency (SSCE), osteogenic, adipogenic and chondrogenic differentiation capacity in vitro. Alkaline phosphatase (ALP) activity, mineralization, Oil Red O content, proteoglycan- and collagen type II deposition were quantified. While CFU-F frequency was maintained, SSCE and early proliferation rate decreased significantly with advanced donor age. MSC with higher proliferation rate before start of induction showed stronger osteogenic, adipogenic and chondrogenic differentiation. MSC with high osteogenic capacity underwent better chondrogenesis and showed a trend to better adipogenesis. Lineage choice was, however, unaltered with age. CONCLUSION: Ageing influenced activation from dormancy and replicative function of MSC in a way that it may be more demanding to mobilize MSC to fast cell growth at advanced age. Since fast proliferation came along with high multilineage capacity, the proliferation status of expanded MSC rather than donor age may provide an argument to restrict MSC-based therapies to certain individualsKeywords
This publication has 40 references indexed in Scilit:
- Mesenchymal and haematopoietic stem cells form a unique bone marrow nicheNature, 2010
- What old means to boneTrends in Endocrinology & Metabolism, 2010
- Donor sex and age influence the chondrogenic potential of human femoral bone marrow stem cellsOsteoarthritis and Cartilage, 2010
- Clonal analysis and hierarchy of human bone marrow mesenchymal stem and progenitor cellsExperimental Hematology, 2010
- Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor CellsPLOS ONE, 2009
- Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized ProcessPLOS ONE, 2008
- Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapiesMechanisms of Ageing and Development, 2008
- Age‐related intrinsic changes in human bone‐marrow‐derived mesenchymal stem cells and their differentiation to osteoblastsAging Cell, 2008
- Chondrogenic Potential of Human Adult Mesenchymal Stem Cells Is Independent of Age or Osteoarthritis EtiologyThe International Journal of Cell Cloning, 2007
- Aging bone and cartilage: cross-cutting issuesBiochemical and Biophysical Research Communications, 2004