Extracellular vesicles derived from bone marrow mesenchymal stem cells as pro-osteogenic agents: elucidating the role of mitochondrial metabolism in bone regeneration

Abstract

Bone regeneration is a major clinical problem, and there is a need for novel and innovative therapeutic approaches. Mesenchymal stem cells (MSCs) are promising but are limited by issues of cell delivery and reproducibility. Therefore, there is a focus on the secreted extracellular vesicles (EVs) of MSCs, which contain bioactive molecules that could potentially mimic the beneficial effects of MSCs (Biswas et al., 2025; Anand, Komath and Urulangodi, 2026). In this study, the osteogenic properties of EVs derived from rat bone marrow-derived MSCs (rBMSC-EVs) were explored. The rBMSC-EVs promoted proliferation and osteogenic differentiation of progenitor cells in vitro, even in the absence of chemical inducers. A comparative proteomic analysis showed that proteins in the rBMSC-EVs were enriched for those involved in angiogenesis, tissue regeneration, and osteogenesis, together with factors involved in mitochondrial aerobic respiration and the electron transport chain (Takafuji et al., 2020; Chakrabarty and Chandel, 2021; Smith and Eliseev, 2021). Functional studies showed that EV treatment led to a significant increase in mitochondrial respiration and biogenesis in target cells, thus providing a mechanistic explanation for the high energy demand of bone regeneration. In summary, the data provide evidence for rBMSC-EVs as a novel and promising cell-free therapeutic agent for bone regeneration, with therapeutic effects mediated by metabolic reprogramming, thus providing a framework for EV-based orthopaedic therapeutics.

Cite: Anand GG, Gopala S, Urulangodi M, Komath M (2026) Extracellular vesicles derived from bone marrow mesenchymal stem cells as pro-osteogenic agents: elucidating the role of mitochondrial metabolism in bone regeneration. BEC prep 2026.6 https://doi.org/10.26124/becprep.2026-0006