Lui Pauline Po Yee, Kong Siu Kai, Lau Pui Man, Wong Yin Mei, Lee Yuk Wa, Tan Chunlai, Wong On Tik
1 Headquarter, Hospital Authority , Hong Kong SAR, China .
Tissue Eng Part A. 2014 Nov;20(21-22):3010-20. doi: 10.1089/ten.TEA.2013.0714. Epub 2014 Jun 16.
The immunogenicity of tendon-derived stem cells (TDSCs) has implications for their clinical use for the promotion of tendon repair. The immunogenicity and escape mechanisms of rat patellar TDSCs were examined after allogeneic transplantation. Our results showed that TDSCs exhibited low immunogenicity as evidenced by the following: (i) the incubation of target TDSCs with immunized serum did not show antibody recognition and did not induce the complement-dependent cytotoxicity; (ii) target TDSCs elicited a very low level of lymphocyte proliferation and did not exhibit host lymphocyte-mediated cytotoxicity; and (iii) target TDSCs dose dependently suppressed the phorbol 12-myristate 13-acetate (PMA)- and ionomycin-induced host lymphocyte proliferation. For the mechanistic studies, TDSCs expressed major histocompatibility complex (MHC)-I but a very low level of MHC-II, CD86 and CD80 for the induction of T-cell response. Also, TDSCs were found to express intracellular Fas and FasL. γ-IFN pretreatment did not increase the level of MHC-II and CD86 for the upregulation of immune response. Moreover, the immunosuppressive mediators indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta 1 (TGF-β1) were found not to be involved in the escape mechanism of target TDSCs from host lymphocyte attack. In conclusion, allogeneic TDSCs exhibited low immunogenicity. Allogeneic TDSCs might be used for transplantation.
肌腱来源干细胞(TDSCs)的免疫原性对其促进肌腱修复的临床应用具有重要意义。在同种异体移植后,对大鼠髌腱TDSCs的免疫原性及逃逸机制进行了研究。我们的结果表明,TDSCs表现出低免疫原性,具体如下:(i)将靶TDSCs与免疫血清孵育未显示抗体识别,也未诱导补体依赖性细胞毒性;(ii)靶TDSCs引发的淋巴细胞增殖水平极低,且未表现出宿主淋巴细胞介导的细胞毒性;(iii)靶TDSCs剂量依赖性地抑制佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯(PMA)和离子霉素诱导的宿主淋巴细胞增殖。对于机制研究,TDSCs表达主要组织相容性复合体(MHC)-I,但MHC-II、CD86和CD80的表达水平极低,难以诱导T细胞反应。此外,发现TDSCs表达细胞内Fas和FasL。γ-干扰素预处理并未增加MHC-II和CD86的水平以上调免疫反应。此外,发现免疫抑制介质吲哚胺2,3 - 双加氧酶(IDO)和转化生长因子-β1(TGF-β1)不参与靶TDSCs逃避宿主淋巴细胞攻击的机制。总之,同种异体TDSCs表现出低免疫原性。同种异体TDSCs可能可用于移植。