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Induced Mesenchymal Stem Cells: A Promising New Treatment Strategy for Inflammatory Bowel Disease?

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Review of “Mesenchymal Stem Cells Derived from iPSC Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Due to their inherent immunomodulatory and anti-inflammatory properties, mesenchymal stem cells (MSCs) have emerged as a promising new treatment strategy for inflammatory bowel disease (IBD) [1]. Obstacles to autologous therapy include cell source, donor age, and intrinsic MSC variability; however, many have posited the derivation of MSCs from induced pluripotent stem cells (iPSCs) as a potential solution to these problems and studies have already investigated the ability of induced (i)MSCs to suppress inflammation in mouse models [2-4].

Now, a new STEM CELLS Translational Medicine study from the laboratory of Steven Dow (Colorado State University, Fort Collins, CO, USA) describes the effectiveness of treatment with iMSCs compared to adipose-derived MSCs (adMSCs) in an induced colitis mouse model of human IBD [5]. 

Supplementation of dextran sodium sulfate (DSS) in drinking water induced clinical signs consistent with colitis, including weight loss, bloody diarrhea, and abnormal fecal consistency. Both iMSC and adMSC treatment helped to reverse these IBD-related pathologies to a similar degree and reduce lesion scores and inflammation in the gut. In-depth analyses indicated that iMSC treatment also increased intestinal epithelial cell proliferation, Lgr5+ intestinal stem cell number, and intestinal angiogenesis.

The low overall numbers of MSCs detected in colonic tissues suggested that these improvements derived from the secretion of paracrine acting factors rather than direct cell-to-cell effects between MSC and colonic epithelial cells, and this mode-of-action necessitated repeated MSC injections to provide long-term therapeutic effects. Most interestingly, a study of the microbiome of model mice revealed that iMSC or adMSC treatment returned the microbial environment of mice with colitis to that resembling healthy mice, thereby improving overall intestinal health and healing.

The results of this exciting new study have already led the authors to study iMSC treatment in a spontaneous canine IBD model, based on evidence of efficacy in a similar model [6], as a means to evaluate safety/efficacy in a more translationally relevant setting. Early results suggest safety, with no evidence of teratoma/tumor formation following systemic iMSC administration.

For more on the promise of induced mesenchymal stem cells and stem cell treatments for inflammatory bowel diseases, stay tuned to the Stem Cells Portal.

References

  1. Magro F, Langner C, Driessen A, et al., European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis 2013;7:827-51.
  2. Lian Q, Zhang Y, Zhang J, et al., Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation 2010;121:1113-23.
  3. Lai PL, Lin H, Chen SF, et al., Efficient Generation of Chemically Induced Mesenchymal Stem Cells from Human Dermal Fibroblasts. Sci Rep 2017;7:44534.
  4. Sun YQ, Deng MX, He J, et al., Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic airway inflammation in mice. Stem Cells 2012;30:2692-9.
  5. Sirikul S, Lyndah C, Valerie J, et al., 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. STEM CELLS Translational Medicine 2018;7:456-467.
  6. Perez-Merino EM, Uson-Casaus JM, Duque-Carrasco J, et al., Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Endoscopic and histological outcomes. Vet J 2015;206:391-7.