REVIEW article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1639439
This article is part of the Research TopicTranslation of Mesenchymal Stem Cells in vivo: Evidence from preclinical and clinical testing.View all 5 articles
From Bench to Bedside: Translating Mesenchymal Stem Cell Therapies Through Preclinical and Clinical Evidence
Provisionally accepted
- 1University of Nebraska Medical Center, Nebraska, United States
- 2Penn State Milton S. Hershey Medical Center, Hershey, United States
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Mesenchymal stem cells (MSCs) are emerging as a powerful tool in regenerative medicine due to their ability to differentiate into mesenchymal lineages, such as bone, cartilage, and fat, along with their low immunogenicity and strong immunomodulatory properties. Unlike traditional cell therapies that rely on engraftment, MSCs primarily function through paracrine signalingsecreting bioactive molecules like vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and exosomes. These factors contribute to tissue repair, promote angiogenesis, and modulate immune responses in damaged or inflamed tissues. Recent studies have identified mitochondrial transfer as a novel therapeutic mechanism, where MSCs donate mitochondria to injured cells, restoring their bioenergetic function. This has expanded the therapeutic potential of MSCs to include conditions such as acute respiratory distress syndrome (ARDS) and myocardial ischemia. Clinically, MSCs have shown efficacy in diseases like graft-versus-host disease (GVHD), Crohn's disease, and COVID-19. Trials such as REMODEL and REMEDY have demonstrated improved clinical outcomes, further validating MSC-based interventions. However, several challenges remain, including variability in cell potency, poor engraftment, and inconsistent results across clinical trials. Advances in genetic engineering such as CRISPRmodified MSCs and biomaterial scaffolds are being developed to enhance therapeutic efficacy and cell survival. Additionally, AI-driven platforms are being utilized to personalize MSC therapy and optimize cell selection.Innovative approaches like 3D bioprinting and scalable manufacturing are paving the way for more consistent and precise therapies. Moving forward, the integration of mechanistic insights with robust quality control and regulatory frameworks essential to translating MSC therapies from bench to bedside and ensuring their reliable application in clinical practice.
Keywords: mesenchymal stem cells (MSCs), paracrine signaling, Immunomodulation, Regulatory, clinical evidence, Regenerative Medicine
Received: 02 Jun 2025; Accepted: 23 Jul 2025.
Copyright: © 2025 Patel, Shukla and Shukla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Manish Shukla, Penn State Milton S. Hershey Medical Center, Hershey, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.