Mesenchymal stem cell therapy for ulcerative colitis: Opportunities and challenges in precision medicine

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease posing a growing global health burden. Current therapies face safety concerns and fail to induce mucosal healing. Mesenchymal stem cell (MSC) therapy has emerged as a promising alternative due to its immunomodulatory and regenerative properties. However, its integration into precision medicine paradigms remains challenging. Methods This review examines the key challenges hindering the clinical translation of MSC therapy for UC and proposes innovative strategies to optimize this cell‐based modality. The analysis is based on a systematic evaluation of the current literature, encompassing the biological properties of MSCs, preclinical studies, clinical trial data, biomanufacturing processes, and emerging technological platforms. Results Our analysis identifies key barriers to precision MSC therapy across biomanufacturing, clinical translation, and mechanistic understanding. To address these challenges, we propose a strategic framework that progresses from challenge identification to developing biological strategies for enhancing MSC potency and homing, streamlining therapeutic workflows, and integrating intelligent systems. Conclusion As a viable therapy for UC, MSC therapy faces significant challenges within the precision medicine paradigm. The convergence of novel approaches with artificial intelligence (AI) is paving the way for precision frameworks, and their rigorous validation through clinical trials will be crucial to delivering reliable, patient‐specific therapies. Highlights Overviews key challenges and innovative strategies in MSC therapy for UC within a precision medicine framework. Examines barriers in MSC biomanufacturing, clinical translation, and host microenvironment adaptation. Highlights emerging approaches, encompassing pharmacological preconditioning, 3D culture, cellular engineering, and advanced delivery platforms to enhance MSC potency and homing. Proposes an integrated roadmap combining standardized workflows, combinatorial regimens, and AI for predictive patient stratification and individualized therapy.