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Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model.

ABSTRACT: Cellular therapy with allogeneic or autologous mesenchymal stem cells (MSC) has emerged as a promising new therapeutic strategy for managing inflammatory bowel disease (IBD). However, MSC therapy ideally requires a convenient and relatively homogenous cell source (typically bone marrow or adipose tissues) and the ability to generate cells with stable phenotype and function. An alternative means of generating allogeneic MSC is to derive them from induced pluripotent stem cells (iPSC), which could in theory provide an indefinite supply of MSC with well-defined phenotype and function. Therefore, we compared the effectiveness of iPSC-derived MSC (iMSC) and adipose-derived MSC (adMSC) in a mouse model of IBD (dextran sodium sulfate-induced colitis), and investigated mechanisms of intestinal protection. We found that iMSC were equivalent to adMSC in terms of significantly improving clinical abnormalities in treated mice and reducing lesion scores and inflammation in the gut. Administration of iMSC also stimulated significant intestinal epithelial cell proliferation, increased in the numbers of Lgr5+ intestinal stem cells, and increased intestinal angiogenesis. In addition, the microbiome alterations present in mice with colitis were partially restored to resemble those of healthy mice following treatment with iMSC or adMSC. Thus, iMSC administration improved overall intestinal health and healing with equivalent potency to treatment with adMSC. This therefore is the first report of the effectiveness of iMSC in the treatment of IBD, along with a description of unique mechanisms of action with respect to intestinal healing and microbiome restoration. Stem Cells Translational Medicine 2018;7:456-467.

SUBMITTER: Soontararak S

PROVIDER: S-EPMC5980202 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model.

Soontararak Sirikul S Chow Lyndah L Johnson Valerie V Coy Jonathan J Wheat William W Regan Daniel D Dow Steven S

Stem cells translational medicine 20180410 6

Cellular therapy with allogeneic or autologous mesenchymal stem cells (MSC) has emerged as a promising new therapeutic strategy for managing inflammatory bowel disease (IBD). However, MSC therapy ideally requires a convenient and relatively homogenous cell source (typically bone marrow or adipose tissues) and the ability to generate cells with stable phenotype and function. An alternative means of generating allogeneic MSC is to derive them from induced pluripotent stem cells (iPSC), which could ...[more]

PMID: 29635868

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Project description:The cells secrete extracellular vesicles (EV) that may have an endosomal origin, or from evaginations of the plasma membrane. The former are usually called exosomes, with sizes ranging from 50 to 100 nm. These EV contain a lipid bilayer associated to membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc.) and proteins may be stored inside. The EV composition depends on the producer cell type and its physiological conditions. Through them, the cells modify their microenvironment and the behavior of neighboring cells. That is accomplished by transferring factors that modulate different metabolic and signaling pathways. Due to their properties, EV can be applied as a diagnostic and therapeutic tool in medicine. The mesenchymal stromal cells (MSC) have immunomodulatory properties and a high regenerative capacity. These features are linked to their paracrine activity and EV secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of EV for the treatment of chronic skin ulcers (CSU) has been proposed. Such sores occur when normal healing does not resolve properly. That is usually due to excessive prolongation of the inflammatory phase. These ulcers are associated with aging and diseases, such as diabetes, so their prevalence is increasing with the one of such latter disease, mainly in developed countries. This has very important socio-economic repercussions. In this review, we show that the application of MSC-derived EV for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the EV have immunosuppressive and immunomodulatory properties. Likewise, they have the ability to activate the angiogenesis, proliferation, migration, and differentiation of the main cell types involved in skin regeneration. They include endothelial cells, fibroblasts, and keratinocytes. Most of the studies carried out so far are preclinical. Therefore, there is a need to advance more in the knowledge about the conditions of production, isolation, and action mechanisms of EV. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.

Dataset Information

Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model.

Publications

Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model.

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