METHODS: In the current study, healthy mesenchymal stem/stromal cells derived from iPSCs (iMSCs) expressing ACVR2B-Fc (iMSCACVR2B-Fc), which is a neutralizing receptobody, were constructed. Furthermore, patient-derived iMSCs and FOP mouse model (ACVR1R206H, female) were used to confirm the inhibitory function of ACVR2B-Fc fusion protein secreted by iMSCACVR2B-Fc on BMP signaling pathways and HO development, respectively.
RESULTS: We found that secreted ACVR2B-Fc attenuated BMP signaling initiated by Activin-A and BMP-9 in both iMSCs and FOP-iMSCs in vitro. Transplantation of ACVR2B-Fc-expressing iMSCs reduced primary HO in a transgenic mouse model of FOP. Notably, a local injection of ACVR2B-Fc-expressing iMSCs and not an intraperitoneal injection improved the treadmill performance, suggesting compound effects of ACVR2B-Fc and iMSCs.
CONCLUSIONS: These results offer a new perspective for treating FOP through stem cell therapy.
方法:在目前的研究中,源自表达ACVR2B-Fc(iMSCACVR2B-Fc)的iPSCs(iMSCs)的健康间充质干细胞/基质细胞,这是一个中和的接受体,是建造的。此外,患者来源的iMSCs和FOP小鼠模型(ACVR1R206H,雌性)用于证实iMSCACVR2B-Fc分泌的ACVR2B-Fc融合蛋白对BMP信号通路和HO发育的抑制功能,分别。
结果:我们发现分泌的ACVR2B-Fc在体外减弱iMSC和FOP-iMSC中由激活素A和BMP-9引发的BMP信号传导。表达ACVR2B-Fc的iMSC的移植减少了FOP的转基因小鼠模型中的原代HO。值得注意的是,局部注射表达ACVR2B-Fc的iMSC而不是腹膜内注射改善了跑步机性能,提示ACVR2B-Fc和iMSC的复合作用。
结论:这些结果为通过干细胞疗法治疗FOP提供了新的视角。