Bone marrow stromal cells (BMSCs) in bone engineering: Limitations and recent advances

Bone marrow stromal cells (BMSCs) have been isolated for the first time by Friedenstein et al. and since then have been considered the progenitor cells for the skeletal tissues. Indeed BMSCs are clonogenic, fibroblastic in shape, and can differentiate along multiple lineages such as osteoblasts, chondrocytes, adipocytes, and hematopoiesis-supportive stroma. When implanted in vivo on a three-dimensional bioceramic scaffold into immunocompromised mice, BMSCs form bone and hematopoiesis-supportive stroma. The ease of harvest from a donor bone marrow together with the ability to form bone in vivo make BMSCs ideal for clinical applications. Thus, ex vivo expanded BMSCs have been employed, first in large animal models, then in human clinical trials, to repair large bone segmental defects. Further investigation of the expanded BMSC population led to the observation that in vitro expansion appears a limiting passage: cells tend to senesce and lose their multidifferentiation potential with time in culture. To overcome these limitations, two approaches have been proposed: (1) identification of the appropriate culture conditions to prevent senescence by possibly selecting a subpopulation with stem cell characteristics, and (2) engineering of the cells by transfection with the telomerase gene to prevent cells from telomere shortening and consequent aging.