Are All Cells Created Equal? Novel Cell-Based Regenerative Therapies in Inflammatory Bowel Disease

Regenerative medicine, and in particular cell-based therapies, are under investigation as therapeutics in the management of inflammatory bowel disease, where despite significant advancements in management, prolonged remission is achieved in less than half of patients experiencing these disorders. In contrast to conventional immunomodulatory medications, these therapies are hypothesised to act through multiple pathways including via regenerative mechanisms, which may enable them to break through the current therapeutic ceiling. Potential therapy candidates include mesenchymal stem cells, human amnion epithelial cells, and regulatory T-cells, as well as their derivatives including extracellular vesicles. Extensive preclinical studies have demonstrated the multi-modal nature of these therapies as well as shared and unique properties. Controversy remains regarding contradictory study outcomes and the efficacy of regenerative therapies in human trials. In this narrative review, we first examine the mechanisms of these candidate cell therapies, including signalling via cytokines and extracellular vesicles, and interactions with immune cells, stromal cells, and the microbiome to determine differences and similarities between them. The second part delves into the current state of regenerative and cell-based therapy, focusing on mesenchymal stem cell, human amnion epithelial cell, T regulatory cells, and their respective extracellular vesicles in IBD treatment. Finally, we close by identifying the major literature gaps and barriers to bringing regenerative medicines to clinical use, resulting in recommendations for future research.