Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies

• Published in: Mechanisms of ageing and development Vol. 129; no. 3; pp. 163 - 173
• Main Authors: Stolzing, A., Jones, E., McGonagle, D., Scutt, A.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.03.2008; Elsevier Science
• Subjects: Adolescent; Adult; Aging; Apoptosis; Biological and medical sciences; Biomarkers - analysis; Bone Marrow Cells - chemistry; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Cell Count; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cellular Senescence; Child; Child, Preschool; Development. Metamorphosis. Moult. Ageing; Fundamental and applied biological sciences. Psychology; Heat shock proteins; Human mesenchymal stem cells; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - chemistry; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Middle Aged; Osteogenesis; Oxidative damage; Phenotype; Reactive Oxygen Species - metabolism; Senescence; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Aging; Heat shock proteins; Senescence; Human mesenchymal stem cells; Oxidative damage; Human; Stem cell; Ageing; Vertebrata; Mammalia; Heat shock protein; Bone marrow; Age
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2007.12.002

Human mesenchymal stem cells (hMSC) represent a promising cell-based therapy for a number of degenerative conditions. Understanding the effect of aging on hMSCs is crucial for autologous therapy development in older subject whom degenerative diseases typically afflict. Previous investigations into the effects of aging on hMSC have proved contradictory due to the relative narrow age ranges of subjects assessed and the exclusive reliance of in vitro assays. This study seeks to address this controversy by using a wider range of donor ages and by measuring indices of cellular aging as well as hMSC numbers ex vivo and proliferation rates. CFU-f analysis and flow cytometry analysis using a CD45 low/D7fib +ve/LNGF +ve gating strategy were employed. In addition a variety of markers of cellular aging, oxidative damage and senescence measured. A reduction in CFU-f and CD45 low/D7fib +ve/LNGF +ve cell numbers were noted in adulthood relative to childhood. Indices of aging including oxidative damage, ROS levels and p21 and p53 all increased suggesting a loss of MSC fitness with age. These data suggest that hMSC numbers obtained by marrow aspiration decline with age. Furthermore, there is an age-related decline in overall BM MSC “fitness” which might lead to problems when using autologous aged MSC for cell-based therapies.