Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease
Raghavan Chinnadurai1, Spencer Ng1, Vijayakumar Velu1
1Raghavan Chinnadurai, Spencer Ng, Vijayakumar Velu, Jacques Galipeau, Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States.
Abstract:
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.
Insights
Mesenchymal stromal cells (MSCs) show promise for inflammatory bowel diseases like Crohn's disease and ulcerative colitis. However, animal models and species differences present challenges for translating preclinical findings to human clinical trials.
Area of Science:
- Regenerative Medicine
- Gastroenterology
- Immunology
Background:
- Mesenchymal stromal cells (MSCs) are being investigated for treating inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis.
- While MSC therapy has demonstrated safety in early trials, robust efficacy data from randomized clinical trials are still needed.
- Understanding the mechanisms by which MSCs reduce gut inflammation is crucial for optimizing therapeutic strategies.
Purpose of the Study:
- To review the therapeutic properties of MSCs in preclinical and clinical studies for IBD.
- To discuss the challenges and potential solutions for using animal models in IBD research involving MSCs.
- To evaluate the suitability of translating findings from animal studies to human clinical applications.
Main Methods:
- Review of existing preclinical and clinical literature on MSCs for IBD.
- Analysis of limitations in current animal models of colitis for mimicking human IBD.
- Comparison of MSC functionality across different species (murine vs. human).
Main Results:
- MSC therapy has shown safety in early human trials for IBD.
- Significant challenges exist in developing animal models that accurately reflect human IBD.
- Species-specific differences in MSC function necessitate caution when extrapolating animal data to human trials.
Conclusions:
- Further research is needed to establish the efficacy of MSCs in randomized clinical trials for IBD.
- Development of more relevant animal models is essential for advancing MSC-based therapies.
- Careful consideration of species-specific differences is critical for successful translation of MSC research from bench to bedside.
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