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, 2018, 9601623

Generation and Applications of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells


Generation and Applications of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells

Chengzhu Zhao et al. Stem Cells Int.


Mesenchymal stem cells (MSCs) are adult stem cells with fibroblast-like morphology and isolated from the bone marrow via plastic adhesion. Their multipotency and immunoregulatory properties make MSCs possible therapeutic agents, and an increasing number of publications and clinical trials have highlighted their potential in regenerative medicine. However, the finite proliferative capacity of MSCs limits their scalability and global dissemination as a standardized therapeutic product. Furthermore, adult tissue provenance could constrain accessibility, impinge on cellular potency, and incur greater exposure to disease-causing pathogens based on the donor. These issues could be circumvented by the derivation of MSCs from pluripotent stem cells. In this paper, we review methods that induce and characterize MSCs derived from induced pluripotent stem cells (iPSCs) and introduce MSC applications to disease modeling, pathogenic mechanisms, and drug discovery. We also discuss the potential applications of MSCs in regenerative medicine including cell-based therapies and issues that should be overcome before iPSC-derived MSC therapy will be applied in the clinic.


Figure 1
Figure 1
Derivation of MSCs from iPSCs. (a) Inducing iMSCs from iPSCs by mimicking embryonic development. During embryonic development, MSCs arise from two major sources: mesoderm and neural crest cells (left). Protocols for the induction include specific signals and morphogens that drives the iPSCs to mesoderm/NCC formation and then generate iMSCs (right). LPM: lateral plate mesoderm. (b) Protocols that induce iMSCs from iPSCs through iNCCs result in a homogeneous mesenchymal cell population without contamination of other cellular phenotypes; therefore, when differentiation is complete, no remnants of undifferentiated cells are found. Frozen stocks can be made to use cells of the same quality in order to evaluate reproducibility.
Figure 2
Figure 2
iMSC-based disease modeling and drug discovery of FOP. iMSCs generated from FOP patient-derived iPSC clones (FOP-iMSC) and gene-corrected (rescued) iPSC clones (resFOP-iPSC) could be applied to in vitro disease modeling, drug screening, and in vivo drug efficacy evaluation.

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