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ABSTRACT
Introduction: Advances in immuno-modulatory therapies, including anti-TNF-α therapies, have greatly increased the chance to achieve long-term remission of inflammatory bowel disease (IBD) patients. However, as the importance of mucosal healing has been demonstrated in a number of clinical studies, new cell-based therapies that can regenerate and fully restore the intestinal mucosal functions are currently under development.
Area covered: In this review, we feature the recent challenges of cell-based therapies that are applied to the treatment of IBD. In particular, we will focus on hematopoietic stem cells (HSC), mesenchymal stem cells (MSCs) and intestinal stem cells (ISCs) as the candidate source for cell-based therapy targeted to treat IBD. The current status, as well as the expected advantages and disadvantages of those transplantations will be summarized and discussed.
Expert opinion: Transplantation of HSC, MSC and ISC may have different levels of potential in their ability to exert an immunomodulatory or pro-regenerative effect. Combined cell therapies, such as co-transplantation of MSC and ISC, may provide improved therapeutic outcome compared to transplantation of a single cell population. Those cell-based therapies may not only improve the disease activity or tissue regeneration, but may also have the potential to decrease the risk of developing colitis-associated cancers.
Article highlights
Cell-based therapies using hematopoietic stem cells (HSC), mesenchymal stem cells (MSCs) and intestinal stem cells (ISCs) are under development for inflammatory bowel disease (IBD) patients.
HSC transplantation for refractory Crohn’s disease (CD) has been studied in a phase III trial, which resulted in high incidence of serious adverse events, and failed to prove its clinical benefit.
Phase II trials using autologous as well as allogenic MSCs for luminal and fistulizing CD are ongoing.
Transplantation of ISCs is currently at the experimental level, but the pre-clinical data suggest its promising potential in regeneration of the damaged mucosa.
Combining cell therapies may improve the clinical outcome of refractory IBD patients.This box summarizes key points contained in the article.
Acknowledgements
Authors would like to thank Dr. Hiromichi Shimizu and Dr. Ami Kawamoto for providing excellent pictures.
Declaration of interest
This study was supported by MEXT/JSPS KAKENHI grant number 25293170, grant number 23102003, grant number 15K15286, and grant number 226221307; the Research Center Network Program for Realization of Regenerative Medicine from the Japan Science and Technology Agency (JST) and Japan Agency for Medical Research and Development, AMED; the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development, AMED. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.