脆骨病，医学名称为成骨不全症（osteogenesis imperfecta），是一种少见的先天遗传性骨骼发育障碍性疾病，主要表型为I型胶原合成障碍，发病率约为万分之一，全世界大约有500万病人，目前对这种疾病主要采取预防骨折等对症治疗方法，并无有效的治疗方案。来自美国宾州州立大学医学院的研究人员发现直接将骨髓间质干细胞和作为细胞外基质的I型胶原混合后注射到患有成骨不全症的小鼠（oim）股骨的骨髓腔中，骨髓间质干细胞分化成为成骨细胞和骨细胞并在体内合成高密度新骨，显著改善了小鼠长骨的强度。这说明了用这种策略治疗成骨不全症以及其它间叶干细胞疾病的可行性。
该文的第一作者李锋博士说，“之前关于干细胞移植治疗成骨不全症的研究存在许多不确定的结果，这些研究也未能提供证据证明骨髓间质干细胞能直接分化成成骨细胞和骨细胞。我们小组的研究指出了骨髓间质干细胞通过自身分化为成骨细胞和骨细胞，合成I型胶原以治疗成骨不全症。”
研究人员从正常小鼠分离了骨髓干细胞并标记了GFP绿色荧光蛋白。这样就能够追踪骨髓间质干细胞在体内的分布和变化，并且评价对新骨形成的影响和机理。
这项研究发现并提示着：（1）间质干细胞移植到OIM小鼠的股骨中，在两周后就可以直接参与新骨的形成，在6周后明显改善新骨生成，提高长骨的强度和密度；（2）I 型胶原联合骨髓间质干细胞可以进一步显着增加新骨的形成，表现为在机械负荷破坏试验中有显著的最大负荷力，其原理可能是通过限制移植后骨髓间质干细胞的流失，并提供正常细胞外胶原基质改善正常细胞的环境以促进干细胞的生长和分化；（3）移植后间质干细胞不仅仅直接参与新骨形成，而且可能通过旁分泌效应分泌骨相关的因子刺激内源性的干细胞迁移和分化，达到改善治疗成骨不全症的目的。
英国的Shefelbine的小组研究利用胎血干细胞移植也证实干细胞能够在oim小鼠表达成骨细胞的特异标记蛋白，合成I性胶原并改善小鼠的骨的力学特性。李锋博士另一个研究报告也证实间质干细胞能够通过旁分泌效应分泌VEGF，SDF-1等促进干细胞在靶位募集，并在分化过程中分泌BMP2等促进内源性干细胞的分化。宾州州立大学的研究发现是非常令人兴奋的，给出了在间质干细胞治疗成骨不全症治疗研究中的第一个直接证据，这将在成骨不全症细胞治疗研究中影响深远。（生物谷Bioon.com）
更多细节请联系李锋博士（Email：fengli@psu.edu）
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doi:10.1016/j.bone.2010.05.040
Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta
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Abstract
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 ofBMSCs, 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 six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized 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 thee 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.
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Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.
Vanleene M, Saldanha Z, Cloyd KL, Jell G, Bou-Gharios G, Bassett JH, Williams GR, Fisk NM, Oyen ML, Stevens MM, Guillot PV,Shefelbine SJ.
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