Regenerative medicine for inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is potentially curable by “immune rest” and correction of the genetic predisposition inherent in allogeneic hematopoietic stem cell transplantation. However, balancing risks against benefits remains challenging. Recently, application of mesenchymal stem cells (MSCs) serving as a site-regulated “drugstore” is a new concept which creates the possibility of an alternative treatment for many intractable diseases, such as IBD. Depending on the required function of MSC as a cell provider, immune moderator, and/or trophic resource, MSC therapy should be optimized; surprisingly, therapeutic effects do not always require full engraftment of MSCs, but rely on the capacity of MSCs to inhibit pathogenic immune responses and release trophic factors favoring tissue repair. Therefore, optimization of pleiotropic gut trophic factors produced by MSCs must directly enhance new drug discovery for IBD.Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and their patients. However, the translational arm of stem cell science is in a relatively primitive state. Although several clinical studies using MSCs have been initiated, the early results suggest several inherent problems. In all of them, optimization of MSC therapy appears to be the most urgent problem, to be resolved only by scientifically unveiling the mechanisms of therapeutic action. The authors believe that such information would facilitate the critical steps in the paradigm shift from stem cell biology to regenerative medicine for conquering IBD in near future.