CD90- (Thy-1-) high selection enhances reprogramming capacity of murine adipose-derived mesenchymal stem cells.

CD90- (Thy-1-) high selection enhances reprogramming capacity of murine adipose-derived mesenchymal stem cells.
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DOI:
10.1155/2013/392578
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发表时间:
2013
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影响因子:
--
通讯作者:
Ishii H
Ishii H
中科院分区:
医学4区
文献类型:
--
作者:
Kawamoto K;Konno M;Nagano H;Nishikawa S;Tomimaru Y;Akita H;Hama N;Wada H;Kobayashi S;Eguchi H;Tanemura M;Ito T;Doki Y;Mori M;Ishii H

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背景间充质干细胞(Mesenchymal stem cells,MSCs)是一种多能性的细胞,可以分化为多种具有独特免疫调节功能的细胞。一些临床试验已经证明了MSC在器官移植中的安全性和可能的有效性。因此,干细胞疗法是有希望的耐受诱导。在这项研究中,我们评估了小鼠ADSC的重编程能力,发现最初作为胸腺细胞抗原发现的CD 90(Thy-1)可能是细胞治疗的有用标志物。法从B6小鼠分离鼠ADSC,使用FACSAria细胞分选仪通过选择CD 90 Hi或CD 90 Lo进行分选,然后用四种标准因子(4F; Oct 4、Sox 2、Klf 4和c-Myc)转导。结果使用标准4F转导对未分选的、CD 90 Hi分选的和CD 90 Lo分选的鼠ADSC进行重编程。与CD 90 Lo ADSC相比,CD 90 Hi ADSC显示碱性磷酸酶阳性集落数量增加。未分选、CD 90 Hi分选和CD 90 Lo分选的ADSC的相对重编程效率分别为100%、116.5%和74.7%。CD 90 Hi细胞对重编程更敏感。结论CD 90 Hi ADSCs的重编程能力高于CD 90 Lo ADSCs,表明ADSCs具有异质性亚群。因此,CD 90 Hi选择提供了分离高度抑制性亚群用于基于干细胞的耐受诱导治疗的有效策略。
Background. Mesenchymal stem cells (MSCs), including adipose tissue-derived mesenchymal stem cells (ADSC), are multipotent and can differentiate into various cell types possessing unique immunomodulatory features. Several clinical trials have demonstrated the safety and possible efficacy of MSCs in organ transplantation. Thus, stem cell therapy is promising for tolerance induction. In this study, we assessed the reprogramming capacity of murine ADSCs and found that CD90 (Thy-1), originally discovered as a thymocyte antigen, could be a useful marker for cell therapy. Method. Murine ADSCs were isolated from B6 mice, sorted using a FACSAria cell sorter by selection of CD90Hi or CD90Lo, and then transduced with four standard factors (4F; Oct4, Sox2, Klf4, and c-Myc). Results. Unsorted, CD90Hi-sorted, and CD90Lo-sorted murine ADSCs were reprogrammed using standard 4F transduction. CD90Hi ADSCs showed increased numbers of alkaline phosphatase-positive colonies compared with CD90Lo ADSCs. The relative reprogramming efficiencies of unsorted, CD90Hi-sorted, and CD90Lo-sorted ADSCs were 100%, 116.5%, and 74.7%, respectively. CD90Hi cells were more responsive to reprogramming. Conclusion. CD90Hi ADSCs had greater reprogramming capacity than CD90Lo ADSCs, suggesting that ADSCs have heterogeneous subpopulations. Thus, CD90Hi selection presents an effective strategy to isolate a highly suppressive subpopulation for stem cell-based tolerance induction therapy.
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