Fusion between mesenchymal stem/stromal cells and tissue specific cells as a mechanism of tissue regeneration
TL;DR
The studies on MSC fusion reviewed here suggest the potential of the resulting hybrids for tissue regeneration, particularly in the cardiovascular, muscular, and nervous systems, however, there is also evidence that spontaneous MSC fusion is a rare event.
Abstract
Tissue regeneration is a rigorously regulated physiological process that maintains tissue homeostasis and restores the functionality of injured tissues and organs. Mesenchymal stem/stromal cells (MSCs) play a key role in this process. One of the mechanisms that underpins their regenerative capacity is cell fusion. The fusion of various animal cells is well recognized and established. In contrast, the process of cell fusion between human MSCs and other somatic cell types is poorly understood, particularly regarding the mechanisms that induce membrane merging and the characteristics of the resulting hybrids, such as their regenerative potential. This review aims to systematically evaluate evidence from studies investigating cell fusion between human MSCs and various tissue-specific cells for the purpose of tissue regeneration. The search terms “cell fusion” and “mesenchymal stem cells” or “mesenchymal stromal cells” AND (humans[Filter]) NOT (cancer) were used to search for publications in PubMed, Web of Science, and Scopus in July 2024, with the search updated in June 2026. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting systematic reviews were followed. A total of 206 publications were identified across all three databases. After excluding the studies evaluating osteoclastogenesis, myogenesis, neurogenesis, tumorigenesis, and nonhuman samples, only 47 references remained that addressed the topic of this review, indicating that knowledge of human MSC fusion for regenerative purposes remains limited. Most of the research studies investigated fusion between adult bone marrow (BM)-derived MSCs using an in vitro coculture system to improve cardiac tissue regeneration or to treat Duchenne muscular dystrophy. However, a substantial number of studies provide evidence that fusion is not a mechanism of MSCs plasticity and transdifferentiation. The studies on MSC fusion reviewed here suggest the potential of the resulting hybrids for tissue regeneration, particularly in the cardiovascular, muscular, and nervous systems. However, there is also evidence that spontaneous MSC fusion is a rare event. Further studies evaluating the generation and regenerative potential of the hybrids that possess the best characteristics of both partner cells, such as self-renewal and tissue formation, are of utmost importance for developing advanced therapy medicinal products (ATMPs) for the treatment of genetic and degenerative disorders.