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

Abstract

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.

Extracellular Vesicles from Mesenchymal Stem Cells Exert Pleiotropic Effects on Amyloid‐β, Inflammation, and Regeneration: A Spark of Hope for Alzheimer's Disease from Tiny Structures?

“…In fact, MSCs exert a paracrine activity that involves the secretion of soluble factors, the transfer of mitochondria (mostly occurring by way of tunneling nanotubes), and the release of exosomes or microvesicles (MVs; see Box 3) containing RNA, proteins, and other molecules, which target neighboring cells. [30,31] The successful differentiation of MSCs from human iPSCs and their comparable or even better performances in terms of proliferation, immunomodulation, cytokine profiles, production of EVs, and bioactive secretome [32] are opening a novel perspective in terms of personalized medicine. [33] [24] and following studies.…”

Bone marrow-derived mononuclear cell therapy can attenuate systemic inflammation in rat heatstroke

“…Recently, several facilities established a mesenchymal stem cell bank and are banking these cells for future use in regenerative medicine applications [ 34 ]. Furthermore, a number of studies have reported methods of generating mesenchymal stem cells derived from induced pluripotent stem cells [ 35 ]. We thus believe that the combination of these epoch-making techniques may play a key role in the future application of BMMNC therapy clinically.…”

Bioprocess Development for Human Mesenchymal Stem Cell Therapy Products

“…The development of a standardized process is frustrated by the heterogeneity of MSCs, which are isolated from different donors and different tissues, resulting in variable phenotypes and functions. The heterogeneity of primary MSCs can be avoided by working instead with induced pluripotent stem cells (iPSCs), which can differentiate into MSC-like cells with potent therapeutic properties [87]. However, well-controlled in vitro expansion processes in bioreactors can also help to reduce the batch-to-batch variation often encountered with MSCs, because parameters such as the seeding density, shear stress during cultivation, and cell density at harvest can be monitored and controlled effectively.…”