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PNAS:人类干细胞成功移植至猪体内

2014年06月08日 浏览量: 评论(0) 来源:生物谷 作者:生物谷 责任编辑:admin

生物谷讯/--对于医疗研究人员而言,干细胞疗法有效性的最大挑战是,宿主通常排斥移植细胞。现在,密苏里大学研究人员已经表明,一种新的转基因猪在接受移植细胞后,无排斥反应风险。

宿主对移植细胞的排斥反应是一个巨大的障碍,R. Michael Roberts说:通过建立一种新的转基因猪,接受移植细胞后,无排斥反应,我们可以在干细胞疗法的研究上向前迈出一大步。

在发表的研究中,研究人员团队植入人类多能干细胞至独特的猪中,Prather专门改造了猪的免疫系统,使猪接受所有的移植细胞,并且没有排斥反应。一旦科学家植入细胞,猪没有排斥干细胞,干细胞茁壮成长。Prather说,这一目标成功实现是值得注意的,因为猪比许多其他实验动物更接近人类。

许多医学研究人员更喜欢用猪进行研究,因为他们比其他动物如小鼠和大鼠,在解剖学上更与人类相似,Prather说:猪对健康威胁响应也与人类类似,这意味着研究中所使用的猪对于许多不同的测试和治疗,更有可能具有与人类类似的结果。

doi:10.1073pnas.1406376111
PMC:
PMID:

Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency

Kiho Leea, et al.

Pigs with severe combined immunodeficiency (SCID) may provide useful models for regenerative medicine, xenotransplantation, and tumor development and will aid in developing therapies for human SCID patients. Using a reporter-guided transcription activator-like effector nuclease (TALEN) system, we generated targeted modifications of recombination activating gene (RAG) 2 in somatic cells at high efficiency, including some that affected both alleles. Somatic-cell nuclear transfer performed with the mutated cells produced pigs with RAG2 mutations without integrated exogenous DNA. Biallelically modified pigs either lacked a thymus or had one that was underdeveloped. Their splenic white pulp lacked B and T cells. Under a conventional housing environment, the biallelic RAG2 mutants manifested a “failure to thrive” phenotype, with signs of inflammation and apoptosis in the spleen compared with age-matched wild-type animals by the time they were 4 wk of age. Pigs raised in a clean environment were healthier and, following injection of human induced pluripotent stem cells (iPSCs), quickly developed mature teratomas representing all three germ layers. The pigs also tolerated grafts of allogeneic porcine trophoblast stem cells. These SCID pigs should have a variety of uses in transplantation biology.

 

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