Exosomes and MSC Therapy Emerge as Top Research Frontier in GVHD Treatment

Graft-versus-host disease (GVHD) affects 40–60% of patients undergoing allogeneic hematopoietic cell transplantation and carries mortality rates up to 15%, with long-term non-relapse mortality reaching 40% at 12 years. Mesenchymal stromal cells (MSCs) have attracted substantial interest for their immunomodulatory properties—suppressing T-cell proliferation, inducing regulatory T cells, and dampening dendritic cell activation—making them a promising therapeutic avenue. Despite rapid growth in this field, no comprehensive bibliometric synthesis had previously mapped its global structure and trajectory.

This study retrieved 875 publications from the Web of Science spanning 2010 to 2023 using the search terms 'mesenchymal stem cells' and 'graft-versus-host disease.' CiteSpace was used for co-authorship, citation burst, and dual-map overlay analyses, while VOSViewer visualized country, institution, journal, and keyword networks. The R package bibliometrix enabled thematic evolution mapping and geographic distribution analysis.

Research output grew steadily from 2010 to 2014, continued rising from 2017 to 2021 with a peak of 73 publications per year, despite fluctuations in 2015, 2017, and 2022. Publications originated from 58 countries across 1,418 institutions. The United States led with 216 publications (18.3%), followed by China (197, 16.7%), Germany (93, 7.8%), and Italy (65, 5.5%). The US–China dyad accounted for roughly 35% of global output. Karolinska Institute was the most prolific institution (41 publications), followed by Southern Medical University and Sun Yat-sen University in China. Among journals, Frontiers in Immunology published the most articles (49), while Blood dominated co-citation rankings with 6,614 co-citations.

The most significant emerging trend identified through keyword co-occurrence and citation burst analysis was the rapid rise of extracellular vesicle and exosome-mediated mechanisms as the dominant frontier in MSC-GVHD research. This shift reflects growing evidence that MSCs exert much of their immunomodulatory effect not through direct cell engraftment, but through paracrine signaling via exosomes—nano-sized vesicles carrying bioactive cargo including miRNAs, proteins, and lipids that reprogram immune cell behavior. This mechanistic reframing has significant implications for how MSC-based therapies are designed and delivered.

From a translational standpoint, the findings suggest that exosome-based therapies could offer a cell-free alternative to MSC transplantation, potentially reducing risks associated with live cell administration. However, the bibliometric nature of this study means causal conclusions cannot be drawn, and the analysis is limited to English-language publications on Web of Science, which may underrepresent research from non-English-speaking regions.