Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect
Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect
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DOI：
10.2106/00004623-200310000-00010
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发表时间：
2003-10-01
影响因子：
5.3
通讯作者：
Kadiyala, S
中科院分区：
文献类型：
--
作者：
Arinzeh, TL;Peter, SJ;Kadiyala, S
背景：来自成人骨髓的间充质干细胞是能够形成骨、软骨和其他结缔组织的多能细胞。在以前的研究中，我们证明了自体间充质干细胞可以修复狗的临界大小的骨缺损。本研究的目的是确定是否使用同种异体间充质干细胞可以治愈一个临界大小的骨缺损，在不使用免疫抑制剂therapy.Methods：一个临界大小的节段性骨缺损，21毫米的长度，在中间部分的12只成年狗的股骨干，体重在22和25公斤之间。每一个缺损都用同种异体间充质干细胞治疗，这些细胞被装载到由羟基磷灰石-磷酸三钙组成的中空陶瓷圆柱体上。移植前通过犬白细胞抗原分型确定供体干细胞和受体犬之间完全不匹配。在植入后4周、8周和16周，通过组织学和放射学评价愈合反应。将16周时的放射学和组织学结果与对照缺损的历史数据进行比较，对照缺损包括用装载有自体间充质干细胞的圆柱体治疗的缺损、用不含间充质干细胞的圆柱体治疗的缺损和未治疗的缺损（空的）。全身免疫反应进行了评估，通过分析受体血清生产的抗体对同种异体cells.Results：对于与同种异体间充质干细胞植入物治疗的缺陷，没有不良的主机反应可以检测到在任何时间点。组织学上，未发生淋巴细胞浸润，也未检测到抗同种异体细胞的抗体。在组织学上，8周时，骨痂跨越缺损的长度，并且板层骨填充宿主骨-植入物界面处的植入物的孔隙。还检测到荧光标记的同种异体细胞。在16周时，新骨已经在整个植入物中形成。这些结果与加载有自体细胞的植入物中观察到的结果一致。在16周时，装载同种异体或自体干细胞的植入物在可用孔隙内的骨含量显著高于无细胞植入物（p < 0.05）。结论：本研究的结果表明，装载在羟基磷灰石-磷酸三钙植入物上的同种异体间充质干细胞在不使用免疫抑制治疗的情况下增强了犬股骨中临界尺寸节段性缺损的修复。没有不良的免疫反应被检测到在这个model.Clinical Relevance：使用同种异体间充质干细胞修复大的缺陷可能是一种替代自体和异体骨移植程序。同种异体方法将使间充质干细胞能够从任何供体中分离、扩增和冷冻保存，为骨组织工程提供容易获得的细胞来源。
Background: Mesenchymal stem cells from adult bone marrow are multipotent cells capable of forming bone, cartilage, and other connective tissues. In a previous study, we demonstrated that autologous mesenchymal stem cells could repair a critical-sized bone defect in the dog. The objective of this study was to determine whether the use of allogeneic mesenchymal stem cells could heal a critical-sized bone defect in the femoral diaphysis in dogs without the use of immunosuppressive therapy.Methods: A critical-sized segmental bone defect, 21 mm in length, was created in the mid-portion of the femoral diaphysis of twelve adult dogs that weighed between 22 and 25 kg. Each defect was treated with allogeneic mesenchymal stem cells loaded onto a hollow ceramic cylinder consisting of hydroxyapatite-tricalcium phosphate. A complete mismatch between donor stem cells and recipient dogs was identified by dog leukocyte antigen typing prior to implantation. The healing response was evaluated histologically and radiographically at four, eight, and sixteen weeks after implantation. The radiographic and histological results at sixteen weeks were compared with the historical data for the control defects, which included defects that had been treated with a cylinder loaded with autologous mesenchymal stem cells, defects treated with a cylinder without mesenchymal stem cells, and defects that had been left untreated (empty). The systemic immune response was evaluated by the analysis of recipient serum for production of antibodies against allogeneic cells.Results: For defects treated with allogeneic mesenchymal stem cell implants, no adverse host response could be detected at any time-point. Histologically, no lymphocytic infiltration occurred and no antibodies against allogeneic cells were detected. Histologically, by eight weeks, a callus spanned the length of the defect, and lamellar bone filled the pores of the implant at the host bone-implant interface. Fluorescently labeled allogeneic cells were also detected. At sixteen weeks, new bone had formed throughout the implant. These results were consistent with those seen in implants loaded with autologous cells. Implants loaded with allogeneic or autologous stem cells had significantly greater amounts of bone within the available pore space than did cell-free implants at sixteen weeks (p < 0.05).Conclusions: The results of this study demonstrated that allogeneic mesenchymal stem cells loaded on hydroxyapatite-tricalcium phosphate implants enhanced the repair of a critical-sized segmental defect in the canine femur without the use of immunosuppressive therapy. No adverse immune response was detected in this model.Clinical Relevance: The use of allogeneic mesenchymal stem cells for the repair of large defects may be an alternative to autologous and allogeneic bone-grafting procedures. An allogeneic approach would enable mesenchymal stem cells to be isolated from any donor, expanded, and cryopreserved, providing a readily available source of cells for bone tissue engineering.