Current trends and promising clinical utility of IPSC-derived MSC (iMSC).

Mesenchymal stem cells (MSCs) differentiated from human induced pluripotent stem cells (iPSC) or induced MSC (iMSCs) are expected to address issues of scalability and safety as well as the difficulty in producing homogenous clinical grade MSCs as demonstrated by the promising outcomes from preclinical and clinical trials, currently ongoing. The assessment of iMSCs based in vitro and in vivo studies have thus far showed more superior performance as compared to that of the primary or native human MSCs, in terms of cell proliferation, expansion capacity, immunomodulation properties as well as the influence of paracrine signaling and exosomal influence in cell-cell interaction. In this chapter, an overview of current well-established methods in generating a sustainable source of iMSCs involving well defined culture media is discussed followed by the properties of iMSC as compared to that of MSC and its promising prospects for continuous development into potential clinical grade applications.

Current developments and therapeutic potentials of exosomes from induced pluripotent stem cells-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent cells derived from adult human tissues that have the ability to proliferate in vitro and maintain their multipotency, making them attractive cell sources for regenerative medicine. However, MSCs reportedly show limited proliferative capacity with inconsistent therapeutic outcomes due to their heterogeneous nature. On the other hand, induced pluripotent stem cells (iPSC) have emerged as an alternative source for the production of various specialized cell types via their ability to differentiate from all three primary germ layers, leading to applications in regenerative medicine, disease modeling, and drug therapy. Notably, iPSCs can differentiate into MSCs in monolayer, commonly referred to as induced mesenchymal stem cells (iMSCs). These cells show superior therapeutic qualities compared with adult MSCs as the applications of the latter are restricted by passage number and autoimmune rejection when applied in tissue regeneration trials. Furthermore, increasing evidence shows that the therapeutic properties of stem cells are a consequence of the paracrine effects mediated by their secretome such as from exosomes, a type of extracellular vesicle secreted by most cell types. Several studies that investigated the potential of exosomes in regenerative medicine and therapy have revealed promising results. Therefore, this review focuses on the recent findings of exosomes secreted from iMSCs as a potential noncell-based therapy.

The study of cancer cell in stromal environment through induced pluripotent stem cell-derived mesenchymal stem cells.

BACKGROUND: The development of mesenchymal stem cells (MSCs) has gained reputation from its therapeutic potential in stem cell regeneration, anti-inflammation, tumor suppression, and drug delivery treatment. Previous studies have shown MSCs have both promoting and suppressing effects against cancer cells. While the limitation of obtaining a large quantity of homologous MSCs for studies and treatment remains a challenge, an alternative approach involving the production of MSCs derived from induced pluripotent stem cells (iPSCs; induced MSCs [iMSCs]) may be a promising prospect given its ability to undergo prolonged passage and with similar therapeutic profiles as that of their MSC counterparts. However, the influence of iMSC in the interaction of cancer cells remains to be explored as such studies are not well established. In this study, we aim to differentiate iPSCs into MSC-like cells as a potential substitute for adult MSCs and evaluate its effect on non-small-cell lung cancer (NSCLC). METHODS: iMSCs were derived from iPSCs and validated with reference to the International Society of Cellular Therapy guidelines on MSC criteria. To create a stromal environment, the conditioned medium (CM) of iMSCs was harvested and applied for coculturing of NSCLC of H1975 at different concentrations. The H1975 was then harvested for RNA extraction and subjected to next-generation sequencing (NGS) for analysis. RESULTS: The morphology of iMSCs-CM-treated H1975 was different from an untreated H1975. Our NGS data suggest the occurrence of apoptotic events and the presence of cytokines from H1975's RNA that are treated with iMSCs-CM. CONCLUSION: Our results have shown that iMSCs may suppress the growth of H1975 by releasing proapoptotic cytokines into coculture media. Using iPSC-derived MSC models allows a deeper study of tumor cross talk between MSC and cancer cells that can be applied for potential future cancer therapy.