Understanding the Potential of Mesenchymal Stem Cells for Clinical Use

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Mesenchymal stem cells (MSCs) have gained remarkable interest in the field of regenerative medicine because of their innate high proliferation ability, paracrine effects, multipotent differentiation potential, and immunomodulatory properties. Autologous bone marrow aspirate has been the gold standard source for MSCs. However, the number of MSCs in BMA has been shown to decline with age, warranting cell expansion to achieve therapeutic efficiency. Additionally, the efficacy of MSCs is dependent on several factors such as source of MSCs, viability of MSCs after implantation, potency of MSCs, and severity of the disease condition.1 One of the major limitations of cell therapy is the loss of cell viability that may occur shortly after implantation. This shortcoming can potentially be resolved by (A) in vitro priming of MSCs to make them potent enough that paracrine effects trigger the tissue regenerative cascade, and (B) optimization of the delivery mechanism of MSCs to enhance cell viability.
In vitro priming of MSCs may be accomplished by predisposing them to survive in hypoxic and ischemic conditions commonly seen with bone defects. Growth factors and cytokines have been shown to direct MSC fate. However, increased costs due to use of recombinant proteins, failure to capture the complex microenvironment of the native extracellular matrices (ECM), and inadequate knowledge of required dosage are some of the shortcomings of this approach. Cell-secreted ECMs have been shown to possess the underlying structure and trophic factors needed to facilitate MSC attachment and differentiation.2 ECM-coated microcarrier beads incorporated within alginate hydrogels have been used to promote osteogenesis with MSCs.3 Additionally, it has been shown that the survival and osteogenic potential of MSCs can be improved by the formation of three-dimensional spheroids compared with monolayer culturing of MSCs.4 MSCs cultured by this method were shown to have significantly higher vascular endothelial growth factor secretion and to better resist apoptosis posttransplantation compared with dissociated MSCs.
MSCs have a promising role in cell therapy for the treatment of various disorders. However, many challenges remain in making this cell population safe and effective. It is important to select optimal cell sources, culture conditions, scaffolding materials, and delivery methods to overcome the challenges associated with MSCs.

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