) a+ S* K+ e& L G. ?6 f1 y * E# [ z/ a- E0 B$ _1 ^iPSC研究依然是朝阳领域 : [, `6 y, U$ S3 N: D ' ?. ^: g5 s# H毋庸置疑，这项研究对整个再生医学领域造成巨大的震动，许多该领域的科学家们都表示这项研究颠覆了之前的观点，影响深远，那么作为作者，徐洋教授是如何看待的呢？ : r( V' Y" K$ F$ Q* R8 S: T6 e/ y) z+ U- {9 l
徐教授表示，“来自中国和日本的科学家们在将iPSC基础治疗投向临床应用的研究中作出了许多努力。我们的这项研究就iPSCs在人类治疗中的安全性问题，提出了一个及时的警告，因为这种免疫原性实际上说明了iPSCs在遗传和表观遗传上的异常。虽然这一结论看上去比较负面，但这是iPSCs应用到人类治疗之前，必须解决的重要问题，这也能避免整个领域的倾覆，就像基因治疗领域出现的未成熟不安全临床应用一样。”2 R* q' G4 K r* D/ L2 D1 {% P
( ?5 f) X& A$ l) p Y) f9 R对于iPSC研究领域来说，虽然近期获得了许多包括这项研究在内的一些负面发现，比如iPS细胞与胚胎干细胞的区别，但是徐教授依然认为这一领域是朝阳领域，他从一位专业学者的角度指出，“iPSC生物学是一个令人激动的研究领域，在人类疾病模型和治疗方面具有巨大的潜力；但这也是一个非常年轻的领域，存在许多未知因素，需要我们探索。在研究探索iPSCs的过程中，也要进行人类干细胞的研究，后者将有助于加深对于iPSC的了解。” 1 _* T: H% f8 e/ \& e; x X; f: Y& J
如需了解徐洋教授实验室更多情况，请登录：http://biology.ucsd.edu/faculty/xu.html。" `) E* a: U- H7 P; ] b- z
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Immunogenicity of induced pluripotent stem cells , W8 U- _& u6 O0 L2 W9 U$ m' w1 u3 \, [
Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as the renewable source of autologous cells1, 2, 3, 4, 5. Whereas it has been generally assumed that these autologous cells should be immune-tolerated by the recipient from whom the iPSCs are derived, their immunogenicity has not been vigorously examined. We show here that, whereas embryonic stem cells (ESCs) derived from inbred C57BL/6 (B6) mice can efficiently form teratomas in B6 mice without any evident immune rejection, the allogeneic ESCs from 129/SvJ mice fail to form teratomas in B6 mice due to rapid rejection by recipients. B6 mouse embryonic fibroblasts (MEFs) were reprogrammed into iPSCs by either retroviral approach (ViPSCs) or a novel episomal approach (EiPSCs) that causes no genomic integration. In contrast to B6 ESCs, teratomas formed by B6 ViPSCs were mostly immune-rejected by B6 recipients. In addition, the majority of teratomas formed by B6 EiPSCs were immunogenic in B6 mice with T cell infiltration, and apparent tissue damage and regression were observed in a small fraction of teratomas. Global gene expression analysis of teratomas formed by B6 ESCs and EiPSCs revealed a number of genes frequently overexpressed in teratomas derived from EiPSCs, and several such gene products were shown to contribute directly to the immunogenicity of the B6 EiPSC-derived cells in B6 mice. These findings indicate that, in contrast to derivatives of ESCs, abnormal gene expression in some cells differentiated from iPSCs can induce T-cell-dependent immune response in syngeneic recipients. Therefore, the immunogenicity of therapeutically valuable cells derived from patient-specific iPSCs should be evaluated before any clinic application of these autologous cells into the patients 1 ?2 Z: z. I& C& {2 K6 W# z' D1 V& w% [9 r% X
; o1 \9 C+ X2 y* ~0 R, i% h) J5 ^- d 作者: 永远的伊凡 时间: 2011-7-5 15:33