Autologous bone marrow concentrate (BMC) and mesenchymal stem cells (MSCs) have beneficial effects on the healing of bone defects. To address the shortcomings associated with the use of primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been proposed as an alternative. The aim of this study was to investigate the bone regeneration potential of human iMSCs combined with calcium phosphate granules (CPG) in critical-size defects in the proximal tibias of mini-pigs in the early phase of bone healing compared to that of a previously reported autograft treatment and treatment with a composite made of either a combination of autologous BMC and CPG or CPG alone. iMSCs were derived from iPSCs originating from human fetal foreskin fibroblasts (HFFs). They were able to differentiate into osteoblasts in vitro, express a plethora of bone morphogenic proteins (BMPs) and secrete paracrine signaling-associated cytokines such as PDGF-AA and osteopontin. Radiologically and histomorphometrically, HFF-iMSC + CPG transplantation resulted in significantly better osseous consolidation than the transplantation of CPG alone and produced no significantly different outcomes compared to the transplantation of autologous BMC + CPG after 6 weeks. The results of this translational study imply that iMSCs represent a valuable future treatment option for load-bearing bone defects in humans.

自体骨髓浓缩液（BMC）和间充质干细胞（MSCs）对骨缺损的愈合具有有益作用。为了解决与使用原代MSC相关的缺点，已经提出了诱导多能干细胞（iPSC）衍生的MSC（iMSC）作为替代方案。这项研究的目的是与早期报道的相比，研究人iMSC与磷酸钙颗粒（CPG）结合在小型猪近端胫骨近端胫骨临界大小缺损中的骨再生潜力。自体移植治疗和使用由自体BMC和CPG或单独CPG组合而成的复合材料进行治疗。iMSCs源自人类胎儿包皮成纤维细胞（HFF）的iPSC。他们能够在体外分化为成骨细胞，表达大量的骨形态发生蛋白（BMP），并分泌与旁分泌信号相关的细胞因子，例如PDGF-AA和骨桥蛋白。在放射学和组织形态学上，与6周后自体BMC + CPG的移植相比，HFF-iMSC + CPG移植比单独的CPG移植产生明显更好的骨整合，并且没有产生明显不同的结果。这项转化研究的结果表明，iMSCs代表了人类承重骨缺损的一种有价值的未来治疗选择。与6周后自体BMC + CPG的移植相比，HFF-iMSC + CPG移植的骨整合明显好于单独的CPG，并且结局无明显差异。这项转化研究的结果表明，iMSCs代表了人类承重骨缺损的一种有价值的未来治疗选择。与6周后自体BMC + CPG的移植相比，HFF-iMSC + CPG移植的骨整合明显好于单独的CPG，并且结局无明显差异。这项转化研究的结果表明，iMSCs代表了人类承重骨缺损的一种有价值的未来治疗选择。