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<p>Both platelet-rich plasma (PRP) and exosomes derived from bone marrow mesenchymal stem cells (BMSCs) exhibit therapeutic potential for spinal cord injury (SCI). However, the combined application of PRP and BMSCs-derived exosome (PRP-primed BMSCs-EXO, PRP-BMSCs-EXO) has not been reported. This study aimed to investigate whether the combined use confers superior therapeutic effects and to explore the underlying molecular mechanisms. First, we examined the effects of PRP priming on the proliferation and exosome secretion of BMSCs. High-throughput sequencing and RT-qPCR were used to analyze the differential miRNA expression profiles between exosomes from PRP- primed BMSCs (PRP-BMSCs-EXO) and naive BMSCs (BMSCs-EXO). Subsequently, a series of in vitro SCI models were established to evaluate the therapeutic effects of PRP-BMSCs-EXO on SCI. TargetScan, RNAhybrid, GO, KEGG, dual-luciferase reporter assay, RT-qPCR, western blotting (WB), and rescue experiments were performed to explore the roles of miRNAs in PRP-BMSCs-EXO and the associated signaling regulatory mechanisms in SCI. Finally, a series of in vivo SCI models were used to verify the therapeutic efficacy and mechanisms of PRP-BMSCs-EXO in vivo. PRP priming promoted the proliferation and exosome secretion of BMSCs. High-throughput sequencing and RT-qPCR revealed that multiple miRNAs were highly expressed in PRP-BMSCs-EXO compared with BMSCs-EXO, among which miR-29a-3p was the most abundant. In in vitro SCI models, PRP-BMSCs-EXO exerted better therapeutic effects than BMSCs-EXO and PRP. Mechanistically, PRP-BMSCs-EXO may enhance the viability and migration and inhibit the apoptosis and autophagy of pheochromocytoma 12 (PC12) cells by delivering miR-29a-3p, thereby promoting nerve regeneration and SCI repair. Bioinformatic analysis and luciferase assays indicated that PTEN may be a downstream target gene of miR-29a-3p. Rescue experiments confirmed that the miR-29a-3p/PTEN/PI3K/Akt/mTOR axis may mediate the regulatory effects of PRP-BMSCs-EXO on neuronal apoptosis, autophagy, and nerve regeneration in SCI. These findings were further validated in in vivo SCI models. Compared with PRP and BMSC-derived exosomes alone, PRP-primed BMSC-derived exosomes provide superior neuroprotective effects against SCI. PRP-BMSCs-EXO inhibits neuronal apoptosis and autophagy and promotes nerve regeneration via the miR-29a-3p/PTEN/PI3K/Akt/mTOR axis, representing a promising and effective therapeutic strategy for SCI.</p>

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Platelet-rich plasma-primed bone marrow mesenchymal stem cell-derived exosomes inhibit neuronal apoptosis and autophagy, and promote nerve regeneration via the miR-29a-3p/PTEN/PI3K/Akt/mTOR axis after spinal cord injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Yao Yu,
  • Man Fang,
  • Cailiang Shen

摘要

Both platelet-rich plasma (PRP) and exosomes derived from bone marrow mesenchymal stem cells (BMSCs) exhibit therapeutic potential for spinal cord injury (SCI). However, the combined application of PRP and BMSCs-derived exosome (PRP-primed BMSCs-EXO, PRP-BMSCs-EXO) has not been reported. This study aimed to investigate whether the combined use confers superior therapeutic effects and to explore the underlying molecular mechanisms. First, we examined the effects of PRP priming on the proliferation and exosome secretion of BMSCs. High-throughput sequencing and RT-qPCR were used to analyze the differential miRNA expression profiles between exosomes from PRP- primed BMSCs (PRP-BMSCs-EXO) and naive BMSCs (BMSCs-EXO). Subsequently, a series of in vitro SCI models were established to evaluate the therapeutic effects of PRP-BMSCs-EXO on SCI. TargetScan, RNAhybrid, GO, KEGG, dual-luciferase reporter assay, RT-qPCR, western blotting (WB), and rescue experiments were performed to explore the roles of miRNAs in PRP-BMSCs-EXO and the associated signaling regulatory mechanisms in SCI. Finally, a series of in vivo SCI models were used to verify the therapeutic efficacy and mechanisms of PRP-BMSCs-EXO in vivo. PRP priming promoted the proliferation and exosome secretion of BMSCs. High-throughput sequencing and RT-qPCR revealed that multiple miRNAs were highly expressed in PRP-BMSCs-EXO compared with BMSCs-EXO, among which miR-29a-3p was the most abundant. In in vitro SCI models, PRP-BMSCs-EXO exerted better therapeutic effects than BMSCs-EXO and PRP. Mechanistically, PRP-BMSCs-EXO may enhance the viability and migration and inhibit the apoptosis and autophagy of pheochromocytoma 12 (PC12) cells by delivering miR-29a-3p, thereby promoting nerve regeneration and SCI repair. Bioinformatic analysis and luciferase assays indicated that PTEN may be a downstream target gene of miR-29a-3p. Rescue experiments confirmed that the miR-29a-3p/PTEN/PI3K/Akt/mTOR axis may mediate the regulatory effects of PRP-BMSCs-EXO on neuronal apoptosis, autophagy, and nerve regeneration in SCI. These findings were further validated in in vivo SCI models. Compared with PRP and BMSC-derived exosomes alone, PRP-primed BMSC-derived exosomes provide superior neuroprotective effects against SCI. PRP-BMSCs-EXO inhibits neuronal apoptosis and autophagy and promotes nerve regeneration via the miR-29a-3p/PTEN/PI3K/Akt/mTOR axis, representing a promising and effective therapeutic strategy for SCI.