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Study of Telomere Length Reveals Rapid Aging of Human Marrow Stromal Cells following In Vitro Expansion

^a Stem Cell Research Group, Giving for Living Postgraduate Centre, Royal Manchester Children’s Hospital, Manchester, United Kingdom;
^b Laboratory Medicine, Stepping Hill Hospital, Poplar Grove, Stockport, United Kingdom;
^c Willink Biochemical Genetics Unit, Royal Manchester Children’s Hospital, Manchester, United Kingdom;
^d Cancer Research UK Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom

Key Words. Mesenchymal stem cells • Transplantation

Correspondence: Ilaria Bellantuono, Ph.D., Stem Cell Research Group, Giving for Living Postgraduate Centre, Royal Manchester Children’s Hospital, Manchester, United Kingdom, M27 4HA. Telephone: 44-161-7272385; Fax: 44-161-7272679; e-mail: Ilaria.Bellantuono{at}cmmc.nhs.uk

Human marrow stromal cells (MSCs) can be isolated from bone marrow and differentiate into multiple tissues in vitro and in vivo. These properties make them promising tools in cell and gene therapy. The lack of a specific MSC marker and the low frequency of MSCs in bone marrow necessitate their isolation by in vitro expansion prior to clinical use. This may severely reduce MSC proliferative capacity to the point that the residual proliferative potential is insufficient to maintain long-term tissue regeneration upon reinfusion. In this study we determined the effect of in vitro expansion on the replicative capacity of MSCs by correlating their rate of telomere loss during in vitro expansion with their behavior in vivo. We report that even protocols that involve minimal expansion induce a rapid aging of MSCs, with losses equivalent to about half their total replicative lifespan.

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