Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
Stem Cells Transl Med. 2019 Jun;8(6):593-605. doi: 10.1002/sctm.18-0199. Epub 2019 Feb 26.
Stem cell-derived exosomes have exhibited promise for applications in tissue regeneration. However, one major problem for stem cell-derived exosome therapies is identifying appropriate source cells. In the present study, we aimed to compare the bone regenerative effect of exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) derived from type 1 diabetes rats (dBMSC-exos) and exosomes secreted by BMSCs derived from normal rats (nBMSC-exos). BMSCs were isolated from rats with streptozotocin-induced diabetes and normal rats. dBMSC-exos and nBMSC-exos were isolated by an ultracentrifugation method and identified. The effects of dBMSC-exos and nBMSC-exos on the proliferation and migration of BMSCs and human umbilical vein endothelial cells (HUVECs) were investigated. The effects of exosomes on the osteogenic differentiation of BMSCs and the angiogenic activity of HUVECs were compared. Finally, a rat calvarial defect model was used to compare the effects of exosomes on bone regeneration and neovascularization in vivo. In vitro, dBMSC-exos and nBMSC-exos both enhanced the osteogenic differentiation of BMSCs and promoted the angiogenic activity of HUVECs, but nBMSC-exos had a greater effect than dBMSC-exos. Similarly, in vivo, both dBMSC-exos and nBMSC-exos promoted bone regeneration and neovascularization in rat calvarial defects, but the therapeutic effect of nBMSC-exos was superior to that of dBMSC-exos. The present study demonstrates for the first time that the bone regenerative effect of exosomes derived from BMSCs is impaired in type 1 diabetes, indicating that for patients with type 1 diabetes, the autologous transplantation of BMSC-exos to promote bone regeneration may be inappropriate. Stem Cells Translational Medicine 2019;8:593-605.
干细胞衍生的外泌体在组织再生应用中显示出了前景。然而，干细胞衍生的外泌体疗法的一个主要问题是确定合适的源细胞。在本研究中，我们旨在比较来源于 1 型糖尿病大鼠的骨髓间充质干细胞（BMSC）分泌的外泌体（dBMSC-exos）和来源于正常大鼠的 BMSC 分泌的外泌体（nBMSC-exos）的骨再生作用。BMSC 从链脲佐菌素诱导的糖尿病大鼠和正常大鼠中分离得到。通过超速离心法分离 dBMSC-exos 和 nBMSC-exos 并进行鉴定。研究了 dBMSC-exos 和 nBMSC-exos 对 BMSC 和人脐静脉内皮细胞（HUVEC）增殖和迁移的影响。比较了外泌体对 BMSC 成骨分化和 HUVEC 血管生成活性的影响。最后，建立大鼠颅骨缺损模型比较外泌体对体内骨再生和血管新生的影响。体外实验结果显示，dBMSC-exos 和 nBMSC-exos 均增强了 BMSC 的成骨分化，促进了 HUVEC 的血管生成活性，但 nBMSC-exos 的作用强于 dBMSC-exos。同样，体内实验结果显示，dBMSC-exos 和 nBMSC-exos 均促进了大鼠颅骨缺损处的骨再生和血管新生，但 nBMSC-exos 的治疗效果优于 dBMSC-exos。本研究首次证明了来源于 BMSC 的外泌体的骨再生作用在 1 型糖尿病中受损，这表明对于 1 型糖尿病患者，自体移植 BMSC-exos 以促进骨再生可能不合适。Stem Cells Translational Medicine 2019;8:593-605.
