Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, PR China.
Biomaterials. 2013 Apr;34(11):2655-64. doi: 10.1016/j.biomaterials.2013.01.004. Epub 2013 Jan 21.
Adipose tissue derived stem cells (ASCs) based therapies for the repair and regeneration of various tissues have been widely investigated recently because of their multilineage potential and self-renewal capability. Our previous study demonstrated that autologous ASCs loaded onto natural coral scaffolds could repair cranial critical-sized defects (CSDs) in a canine model. The objective of this study was to determine whether the use of allogeneic ASCs could heal the same defect without the use of immunosuppressive therapy. The pedigree mismatch, mixed lymphocyte reaction assays (MLRs) and allogeneic skin graft experiments were performed to confirm unrelated ASC donors and recipients. A total of 12 adult Beagle dogs were enrolled in this study and divided into two groups. Bilateral cranial CSDs were created in each animal. The right-side defect was treated with allogeneic ASCs delivered onto a coral scaffold, and the left defect was either filled with an autologous ASC/coral composite (Group 1, n = 5) or with one coral scaffold alone (Group 2, n = 5). The systematic immune response and bone healing were evaluated postoperatively. The results showed that allogeneic ASC transplantation did not induce a systemic immune response by the hosts, and allogeneic ASCs could repair the cranial CSDs in an analogous way to that of the autologous cells. Moreover, both the green fluorescently labeled allogeneic and autologous ASCs were detected within the lacunae of newly formed bone in the defect site at 24 weeks, illustrating that the grafted ASCs contributed directly to bone regeneration in vivo. Thus, we concluded that allogeneic ASCs have the capacity to regenerate bone within craniofacial defects, providing an alternative source of seed cells for bone tissue engineering.
脂肪组织来源的干细胞(ASCs)具有多向分化潜能和自我更新能力,最近被广泛研究用于各种组织的修复和再生。我们之前的研究表明,自体 ASC 负载在天然珊瑚支架上可修复犬模型中的颅部临界尺寸缺损(CSD)。本研究的目的是确定是否可以使用同种异体 ASC 修复相同的缺陷而无需免疫抑制治疗。通过谱系错配、混合淋巴细胞反应(MLR)和同种异体皮肤移植实验,确认了无关 ASC 供体和受者。本研究共纳入 12 只成年比格犬,分为两组。每只动物双侧颅部均创建 CSD。右侧缺损用负载在珊瑚支架上的同种异体 ASC 治疗,左侧缺损用自体 ASC/珊瑚复合物(第 1 组,n = 5)或单独珊瑚支架(第 2 组,n = 5)填充。术后评估系统免疫反应和骨愈合情况。结果表明,同种异体 ASC 移植不会引起宿主的全身免疫反应,同种异体 ASC 可以以类似于自体细胞的方式修复颅部 CSD。此外,在 24 周时,在缺陷部位新形成骨的腔隙中均检测到绿色荧光标记的同种异体和自体 ASC,表明移植的 ASC 直接有助于体内骨再生。因此,我们得出结论,同种异体 ASC 具有在颅面缺损中再生骨的能力,为骨组织工程提供了一种替代的种子细胞来源。