Mesenchymal progenitors show great promise as a cellular therapeutic and for growing new tissues ex vivo for reimplantation. Given that bone marrow and adipose tissue scan be readily harvested in a relatively noninvasive manner, they also serve as a clinically relevant source of autologous starting cells. Moreover, clinical trials have shown the safety of joint injections of allogeneic MSCs in humans,
21 with recent trials showing some evidence of efficacy in some patients, though comprehensive and well-regulated trials are limited.
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However, limitations in this cell type do exist. First, these cells are by definition only multipotent with fixed lineage potential, not totipotent, and so can only differentiate along specific lineages and may not be able to address all tissues in the musculoskeletal system. Additionally, the extent to which they take on the appropriate primary cell phenotype is often limited, where incomplete commitment to the differentiated lineage being a common outcome. For example, if a cell becomes an “inefficient” chondrocyte, production of matrix will only occur under ideal situations, and so in vivo production and survival in the demanding environment of the joint may be compromised.
23 Also, because commitment may be incomplete, this raises the potential for subsequent transition in phenotype after implantation. For example, it has been well documented that MSCs that have undergone in vitro chondrogenesis can transition to an osteogenic phenotype after in vivo implantation.
24 This is compounded by the variation seen in these cell populations both within a single donor, and between individual donors. As every MSC population initiates from a number of different individual cells (that expand into “clones”) and each of these starting cells can have a different potential, the population is by definition heterogeneous.
25 Likewise, between donors, marked variability exists, based on age of donor and other systemic comorbidities that impact the number of resident stem cells. Finally, like primary cells, mesenchymal progenitors are not “true” stem cells and so undergo replicative senescence and loss of potentiality with extended culture expansion.
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