Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4779
Peer-review started: December 9, 2014
First decision: January 22, 2015
Revised: February 13, 2015
Accepted: March 27, 2015
Article in press: March 27, 2015
Published online: April 28, 2015
Utilization of mesenchymal stromal cells (MSCs) for the treatment of Crohn’s disease and ulcerative colitis is of translational interest. Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated. Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials. However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation: (1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases (IBD). The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and (2) Species specific differences in the functionality of MSCs derived from mice versus humans. MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation. Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials. In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD. We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.
Core tip: Several clinical trials have investigated the use of mesenchymal stromal cells (MSCs) for the treatment of inflammatory bowel disease. Although MSC therapy has proven to be safe, efficacy remains to be determined. Animal model studies are necessary to evaluate the efficacy and mechanism of action of MSCs, which will improve ongoing clinical trials. However, clinical translation is largely hampered by (1) variability of colitis animal models available; and (2) differences in the biology of murine and human MSC counterparts. Here we discuss the challenges and approaches of translating animal studies to clinical trials.