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

TLDR

Human marrow stromal cells (MSCs) can be isolated from bone marrow, differentiate into multiple tissues, and are considered promising for cell and gene therapy, but their low frequency and lack of specific markers necessitate in vitro expansion, which may severely diminish their proliferative capacity and impair long‑term tissue regeneration upon reinfusion. This study aimed to determine how in vitro expansion affects MSC replicative capacity by linking telomere attrition rates during culture to their in vivo behavior. The authors measured telomere length loss in MSCs during successive passages and correlated these changes with functional outcomes observed after reinfusion into animal models. They found that even minimal expansion protocols cause rapid MSC aging, with telomere loss equivalent to about half of the cells’ total replicative lifespan.

Abstract

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.