Mechanistic study of locally transplanted bone marrow mesenchymal stem cells combined with erythropoietin in acute spinal cord injury

Background Acute spinal cord injury (SCI) results in irreversible neurological deficits. We hypothesized that local transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with erythropoietin (EPO) would inhibit glial scarring and accelerate functional recovery.Objective To quantify the therapeutic efficacy and underlying mechanisms of BMSCs+EPO versus BMSCs alone in a rat model of acute SCI.Methods Forty SD rats (T10 Allen 60 g·cm impact) were randomized to sham, SCI, SCI+BMSCs, or SCI+BMSCs+EPO (n = 10). BMSCs (5 μL, 2 × 105 cells μL−1) were micro-injected into the lesion epicenter at 1 h post-injury; EPO (5 000 IU kg−1) was given intraperitoneally 1 h after surgery. BBB scores were obtained at 1 d, 2 w and 4 w. Western blot, qPCR, histopathology, immunohistochemistry, ELISA, and in vitro cell viability/CCK-8 assays were performed.Results At 4 weeks, BBB scores in the BMSCs+EPO group reached 12.7 ± 1.5, representing a 54% increase over the BMSCs-alone group (8.3 ± 0.7, p = 0.003) and a 179% increase over the SCI group (4.6 ± 0.6, p < 0.001). Combination therapy significantly reduced glial fibrillary acidic protein (GFAP) and vimentin expression, decreased pro-inflammatory cytokines (IL-1β, TNF-α) and chondroitin-sulfate proteoglycans, while elevating BDNF, GDNF and IGF-1 levels. Histological cavitation was reduced by 42% versus BMSCs alone. In vitro, EPO rescued LPS-induced BMSC death, suppressed astrocyte over-proliferation, and promoted PC12 neurite outgrowth via enhanced BDNF/GDNF secretion.Conclusion BMSCs+EPO exerts synergistic neuroprotective effects, achieving superior locomotor recovery compared with BMSCs monotherapy, and represents a promising adjuvant strategy for acute SCI.