脆骨病,，醫(yī)學(xué)名稱為成骨不全癥（osteogenesis imperfecta）,，是一種少見的先天遺傳性骨骼發(fā)育障礙性疾病,，主要表型為I型膠原合成障礙，發(fā)病率約為萬分之一,，全世界大約有500萬病人,，目前對這種疾病主要采取預(yù)防骨折等對癥治療方法，并無有效的治療方案,。來自美國賓州州立大學(xué)醫(yī)學(xué)院的研究人員發(fā)現(xiàn)直接將骨髓間質(zhì)干細(xì)胞和作為細(xì)胞外基質(zhì)的I型膠原混合后注射到患有成骨不全癥的小鼠（oim）股骨的骨髓腔中,，骨髓間質(zhì)干細(xì)胞分化成為成骨細(xì)胞和骨細(xì)胞并在體內(nèi)合成高密度新骨，顯著改善了小鼠長骨的強(qiáng)度,。這說明了用這種策略治療成骨不全癥以及其它間葉干細(xì)胞疾病的可行性,。
該文的第一作者李鋒博士說，“之前關(guān)于干細(xì)胞移植治療成骨不全癥的研究存在許多不確定的結(jié)果,，這些研究也未能提供證據(jù)證明骨髓間質(zhì)干細(xì)胞能直接分化成成骨細(xì)胞和骨細(xì)胞,。我們小組的研究指出了骨髓間質(zhì)干細(xì)胞通過自身分化為成骨細(xì)胞和骨細(xì)胞，合成I型膠原以治療成骨不全癥,。”
研究人員從正常小鼠分離了骨髓干細(xì)胞并標(biāo)記了GFP綠色熒光蛋白,。這樣就能夠追蹤骨髓間質(zhì)干細(xì)胞在體內(nèi)的分布和變化，并且評價對新骨形成的影響和機(jī)理,。
這項研究發(fā)現(xiàn)并提示著：（1）間質(zhì)干細(xì)胞移植到OIM小鼠的股骨中,，在兩周后就可以直接參與新骨的形成,，在6周后明顯改善新骨生成,，提高長骨的強(qiáng)度和密度；（2）I 型膠原聯(lián)合骨髓間質(zhì)干細(xì)胞可以進(jìn)一步顯著增加新骨的形成,，表現(xiàn)為在機(jī)械負(fù)荷破壞試驗中有顯著的最大負(fù)荷力,，其原理可能是通過限制移植后骨髓間質(zhì)干細(xì)胞的流失，并提供正常細(xì)胞外膠原基質(zhì)改善正常細(xì)胞的環(huán)境以促進(jìn)干細(xì)胞的生長和分化,；（3）移植后間質(zhì)干細(xì)胞不僅僅直接參與新骨形成,，而且可能通過旁分泌效應(yīng)分泌骨相關(guān)的因子刺激內(nèi)源性的干細(xì)胞遷移和分化，達(dá)到改善治療成骨不全癥的目的,。
英國的Shefelbine的小組研究利用胎血干細(xì)胞移植也證實干細(xì)胞能夠在oim小鼠表達(dá)成骨細(xì)胞的特異標(biāo)記蛋白,，合成I性膠原并改善小鼠的骨的力學(xué)特性。李鋒博士另一個研究報告也證實間質(zhì)干細(xì)胞能夠通過旁分泌效應(yīng)分泌VEGF,，SDF-1等促進(jìn)干細(xì)胞在靶位募集,，并在分化過程中分泌BMP2等促進(jìn)內(nèi)源性干細(xì)胞的分化。賓州州立大學(xué)的研究發(fā)現(xiàn)是非常令人興奮的,，給出了在間質(zhì)干細(xì)胞治療成骨不全癥治療研究中的第一個直接證據(jù),，這將在成骨不全癥細(xì)胞治療研究中影響深遠(yuǎn)。（生物谷Bioon.com）
更多細(xì)節(jié)請聯(lián)系李鋒博士（Email：[email protected]）
相關(guān)閱讀
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
Feng Li, Xujun Wang, and Christopher Niyibizi
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.
doi:10.1182/blood-2010-05-287565
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.
doi: 10.1016/j.bbrc.2012.08.095.
Biochem Biophys Res Commun.2012 Oct 5;426(4):475-9.
Differentiating multipotent mesenchymal stromal cells generate factors that exert paracrineactivities on exogenous MSCs: Implications for paracrine activities in bone regeneration.
Li F, Whyte N, Niyibizi C.
