In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells.
In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells.
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体内骨化的体内骨骼通过体外软骨内骨化的骨骼骨化，对成年人和大鼠间充质干细胞的体内造成启动。
DOI：
10.1186/1471-2474-12-31
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发表时间：
2011-01-31
影响因子：
2.3
通讯作者：
van Osch GJ
中科院分区：
文献类型：
--
作者：
Farrell E;Both SK;Odörfer KI;Koevoet W;Kops N;O'Brien FJ;Baatenburg de Jong RJ;Verhaar JA;Cuijpers V;Jansen J;Erben RG;van Osch GJ
肿瘤切除或大面积创伤后需要骨移植来修复大面积骨缺损。可用于这些手术的患者自身骨组织的可用性有限。到目前为止，骨组织工程还没有导致一种植入物，可以用作替代骨置换手术。这主要是由于植入组织的血管化问题导致核心坏死和植入失败。最近发现胚胎干细胞可以通过软骨内分泌途径形成骨，从而将体外产生的软骨在体内转化为骨。在这项研究中，我们研究了人成体间充质干细胞通过软骨内分泌途径形成骨的潜力。在植入之前，将MSC在软骨形成、成骨或对照培养基中培养28天。为了进一步优化这一过程，我们在植入前通过在培养的最后7天内更换成骨培养基来诱导软骨形成结构的矿化。在小鼠皮下植入8周后，在软骨形成培养基中培养的9个构建体中的8个中观察到骨和骨髓形成。在成骨培养基中培养的任何样品中均未观察到骨。转换成骨培养基7天可防止体内骨形成。在培养的最后7天期间向软骨形成培养基中添加β-甘油磷酸盐诱导基质矿化，并且仍然能够在人和大鼠MSC培养物中形成骨和骨髓。为了确定骨是由宿主还是由植入的组织形成，我们使用了免疫活性转基因大鼠模型。因此，我们发现骨中的成骨细胞几乎完全是宿主来源的，但骨细胞是宿主和供体来源的。本手稿中提供的初步数据表明，骨髓间充质干细胞的软骨形成引发导致骨形成在体内使用人类和大鼠细胞。此外，向软骨形成培养基中添加β-甘油磷酸盐不会阻碍该过程。使用转基因动物，我们还证明了宿主和供体细胞在骨形成中发挥了作用。总之，这些数据表明，人MSC的体外软骨分化可能会为骨组织工程提供一种替代且上级的方法。
Bone grafts are required to repair large bone defects after tumour resection or large trauma. The availability of patients' own bone tissue that can be used for these procedures is limited. Thus far bone tissue engineering has not lead to an implant which could be used as alternative in bone replacement surgery. This is mainly due to problems of vascularisation of the implanted tissues leading to core necrosis and implant failure. Recently it was discovered that embryonic stem cells can form bone via the endochondral pathway, thereby turning in-vitro created cartilage into bone in-vivo. In this study we investigated the potential of human adult mesenchymal stem cells to form bone via the endochondral pathway. MSCs were cultured for 28 days in chondrogenic, osteogenic or control medium prior to implantation. To further optimise this process we induced mineralisation in the chondrogenic constructs before implantation by changing to osteogenic medium during the last 7 days of culture. After 8 weeks of subcutaneous implantation in mice, bone and bone marrow formation was observed in 8 of 9 constructs cultured in chondrogenic medium. No bone was observed in any samples cultured in osteogenic medium. Switch to osteogenic medium for 7 days prevented formation of bone in-vivo. Addition of β-glycerophosphate to chondrogenic medium during the last 7 days in culture induced mineralisation of the matrix and still enabled formation of bone and marrow in both human and rat MSC cultures. To determine whether bone was formed by the host or by the implanted tissue we used an immunocompetent transgenic rat model. Thereby we found that osteoblasts in the bone were almost entirely of host origin but the osteocytes are of both host and donor origin. The preliminary data presented in this manuscript demonstrates that chondrogenic priming of MSCs leads to bone formation in vivo using both human and rat cells. Furthermore, addition of β-glycerophosphate to the chondrogenic medium did not hamper this process. Using transgenic animals we also demonstrated that both host and donor cells played a role in bone formation. In conclusion these data indicate that in-vitro chondrogenic differentiation of human MSCs could lead to an alternative and superior approach for bone tissue engineering.
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影响因子：
--
作者：
Farrell, E;O'Brien, FJ;Campbell, VA
通讯作者：
Campbell, VA
影响因子：
2.3
作者：
Unger, Nina J.;Odoerfer, Kathrin I.;Erben, Reinhold G.
通讯作者：
Erben, Reinhold G.
DOI：
10.1002/jor.20816
发表时间：
2009-06
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Coyle CH;Izzo NJ;Chu CR
通讯作者：
Chu CR
影响因子：
--
作者：
Mueller, Michael B.;Tuan, Rocky S.
通讯作者：
Tuan, Rocky S.
影响因子：
64.8
作者：
Chan, Charles K. F.;Chen, Ching-Cheng;Luppen, Cynthia A.;Kim, Jae-Beom;DeBoer, Anthony T.;Wei, Kevin;Helms, Jill A.;Kuo, Calvin J.;Kraft, Daniel L.;Weissman, Irving L.
通讯作者：
Weissman, Irving L.