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

• Published in: Stem cells translational medicine 2018-06, Vol.7 (6), p.456-467
• Main Authors: Soontararak, Sirikul, Chow, Lyndah, Johnson, Valerie, Coy, Jonathan, Wheat, William, Regan, Daniel, Dow, Steven
• Format: Article
• Language: English
• Subjects: Adipose Stem Cells/VSF; Adipose tissue; Adipose Tissue - cytology; Angiogenesis; Animals; Autografts; Bacteria - genetics; Bacteria - isolation & purification; Bone marrow; Cell proliferation; Cell- and Tissue-Based Therapy; Cells, Cultured; Cloning; Colitis; Crohn's disease; Dextran; Dextran Sulfate - toxicity; Digestive Tract Disorders; Digestive Tract Regeneration; Disease Models, Animal; Drinking water; Epithelial cells; Epithelial healing; Feces - microbiology; Female; Genotype & phenotype; Immunoglobulins; Immunology; Immunomodulation; Induced Pluripotent stem cells; Induced Pluripotent Stem Cells - cytology; Inflammation; Inflammation / Inflammatory Disease; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - pathology; Inflammatory Bowel Diseases - therapy; Intestinal Stem Cells / Epithelial Stem Cells; Intestine; Intestines - microbiology; Intestines - physiology; iPSC‐derived mesenchymal stem cell; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Microbiome; Microbiomes; Microbiota; Phenotypes; Pluripotency; Pluripotent Stem Cells; Regeneration; Sodium; Sodium sulfate; Stem cell transplantation; Stem cells; Studies; Translational s and Reviews
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1002/sctm.17-0305

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 Graphical summarizing the effects of stem cell treatment on the colonic tissue, intestinal stem cells, and fecal microbiome