Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression
Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression
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新生儿脱敏支持人胚胎干细胞衍生的间充质干细胞在大鼠关节软骨中的长期存活和功能整合，无需免疫抑制
DOI：
10.1089/scd.2012.0116
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Zou, Xiaohui
中科院分区：
文献类型：
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作者：
Zhang, Shufang;Jiang, Yang Zi;Zou, Xiaohui
免疫反应阻碍了人胚胎干细胞（hESCs）或其衍生物用于体内组织再生的研究。免疫抑制通常在手术后使用，但表现出显着的体重减轻的副作用，并且仅允许短期观察。本研究的目的是探讨新生儿脱敏是否支持hESC-来源的间充质干细胞（hESC-MSCs）的相对长期存活，并促进软骨再生。在大鼠出生当天注射hESC-MSC。新生儿注射后6周，建立全层圆柱形软骨缺损，并移植hESC-MSC-接种的胶原双层支架（d + s + c组）或胶原双层支架（d + s组）。对照组（s + c组）移植hESC-MSC-种植的胶原双层支架。通过组织学分析、免疫组织化学染色和生物力学测试评价软骨再生。通过CD 4免疫染色、细胞死亡检测和再生组织中人细胞的可视化来分析hESC-MSCs在软骨再生中的作用。hESC-MSC表达CD 105、CD 73、CD 90、CD 29和CD 44，但不表达CD 45和CD 34，具有三系分化潜力。d + s + c组的ICRS评分高于d + s组或s + c组。d + s + c组中检测到丰富的II型胶原和改善的机械性能。d + s + c组移植后1周CD 4+炎性细胞浸润和细胞死亡较少，hESC-MSCs存活8周。我们的研究表明，移植前的新生儿脱敏可能是一种有效的方法，以开发一个强大的工具，在动物模型中的人类细胞为基础的治疗的临床前研究。
Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d + s + c) or a collagen bilayer scaffold (group d + s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s + c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d + s + c exhibited greater International Cartilage Repair Society (ICRS) scores than group d + s or group s + c. Abundant collagen type II and improved mechanical properties were detected in group d + s + c. There were less CD4 + inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d + s + c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models.