Therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles against radiation-combined bone injury

To establish a rat model of radiation-combined bone injury (RCBI), evaluate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hUC-MSC-sEVs), and to investigate their role in promoting bone repair.

hUC-MSC-sEVs were isolated via ultracentrifugation and characterized using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. SD rats were randomly divided into three groups:non-ionizing radiation (IR) control group (non-IR), IR model group (IR), and sEVs-treated after IR group (IR+sEV). The RCBI model was established via local irradiation with ⁶⁰Co γ-rays (9.0 Gy) combined with tibial drilling injury. The IR+sEV group received local sEVs injections on days 1 and 8 post-irradiation. Bone repair was dynamically monitored by micro computed tomography (MicroCT) on days 7, 14 and 21 while bone mineral density (BMD), bone volume (BV), and bone surface/volume ratio (BS/BV) were quantitatively analyzed. On day 21, tibial specimens were harvested for hematoxylin-eosin staining and Masson’s Trichrome staining to assess the histomorphological changes.

The isolated sEVs had a mean particle size of approximately 163.4 nm, were typically cup-shaped morphologically, and expressed specific marker proteins-tumor susceptibility gene 101 protein (TSG101) and cluster of differentiation 81 (CD81). Bone repair was significantly delayed in the IR group, with large defects still visible on day 21, but was markedly enhanced in the IR+sEV group, as evidenced by new bone formation observed as early as day 14 and nearly complete defect healing by day 21. Quantitative analysis found that BMD, BV and BS/BV were all significantly superior in the IR+sEV group to those of the IR group (P<0.05). Histological examination revealed that trabecular bone structures were more intact and collagen fibers were more orderly in arrangement in the IR+sEV group.

Human umbilical cord mesenchymal stem cell-derived sEVs can significantly boost the repair of radiation-combined bone injury, which is expected to provide new insight for the biological treatment of radiation-induced bone damage.