Pennsylvania State University College of Medicine, Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Hershey, PA 17033, USA.
Bone. 2010 Sep;47(3):546-55. doi: 10.1016/j.bone.2010.05.040. Epub 2010 Jun 4.
Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At 6 weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solubilized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in three point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation.
目前，关于骨髓基质细胞（BMSCs）在系统性输送到受体动物时对骨形成的贡献，文献中存在相互矛盾的数据。为了了解 BMSCs 是否有助于成骨不全症（OI）骨骼中的骨细胞表型和骨形成，用 GFP 标记的 MSC 直接注入 OI 小鼠模型的股骨中。通过组织学、免疫组织化学和受体骨的生物力学加载来评估细胞对细胞表型和骨形成的贡献。在 BMSC 输注后 2 周，与注射生理盐水的股骨相比，受体股骨的组织学检查显示存在新骨，而注射生理盐水的股骨几乎没有或没有骨形成。新骨中含有很少的供体细胞，如 GFP 荧光所示。在细胞注射后 6 周时，受体股骨中仍可检测到新骨，但注射悬浮在胃蛋白酶溶解的 I 型胶原中的细胞可增强新骨的形成。免疫荧光和免疫组织化学染色显示，新骨中 GFP 阳性的供体细胞与表达骨钙素的细胞定位在一起，表明这些细胞在体内分化为成骨细胞。三点弯曲失效的生物力学加载表明，在 PBS 或可溶性 I 型胶原中输注 BMSC 的股骨比单独注射 PBS 或 I 型胶原的股骨具有更强的生物力学性能。综上所述，这些结果表明移植细胞在体内分化为成骨细胞，并有助于体内骨形成；我们还推测供体细胞在移植后早期诱导内源性细胞的分化或募集，以启动修复过程。
