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异体脂肪来源干细胞,免疫原性低,构建组织工程骨修复猪骨缺损。

Allogeneic adipose-derived stem cells with low immunogenicity constructing tissue-engineered bone for repairing bone defects in pigs.

机构信息

Department 4, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.

出版信息

Cell Transplant. 2012;21(12):2711-21. doi: 10.3727/096368912X654966. Epub 2012 Sep 7.

DOI:10.3727/096368912X654966
PMID:22963757
Abstract

The ideal cells for tissue engineering should have the following characteristics: easy obtainment, safety, immune privilege, the capability of self-renewal, and multipotency. Adipose-derived stem cells (ADSCs) are a promising candidate. However, the immunogenicity of allogeneic mesenchymal stem cells limits their long-term benefits. In this study, we introduced human cytomegalovirus US2/US3 gene into the ADSCs to decrease the expression of MHC I protein of ADSCs and reduce the activation of T-cells of the recipient animals. Moreover, the biosafety and biological characteristics of ADSCs transfected with the US2/US3 genes (ADSCs-US2/US3) were similar to normal ADSCs. Then we took ADSCs-US2/US3 to construct a tissue-engineered bone for repairing bone defects in pigs and found that there were no great differences in repair effects or healing time between the allogeneic ADSCs-US2/US3 group and the autologous ADSC group. These results suggest that allogeneic ADSCs-US2/US3 have the advantages of biological safety, low immunogenicity, and effective osteogenesis. Such barely immunogenic ADSCs will be crucial for the success of future tissue-regenerative approaches.

摘要

用于组织工程的理想细胞应具有以下特征

易于获取、安全、免疫特权、自我更新能力和多能性。脂肪来源的干细胞(ADSCs)是一种很有前途的候选细胞。然而,同种异体间充质干细胞的免疫原性限制了其长期益处。在本研究中,我们将人巨细胞病毒 US2/US3 基因导入 ADSCs 中,以降低 ADSCs 中 MHC I 蛋白的表达,减少受体动物 T 细胞的激活。此外,转染 US2/US3 基因的 ADSCs(ADSCs-US2/US3)的生物安全性和生物学特性与正常 ADSCs 相似。然后,我们使用 ADSCs-US2/US3 构建组织工程骨来修复猪的骨缺损,发现同种异体 ADSCs-US2/US3 组与自体 ADSC 组在修复效果和愈合时间上没有明显差异。这些结果表明,同种异体 ADSCs-US2/US3 具有生物安全性、低免疫原性和有效的成骨作用。这种几乎无免疫原性的 ADSCs 将对未来组织再生方法的成功至关重要。

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