Establishment of novel embryonic stem cell lines derived from the common marmoset (Callithrix jacchus)
Establishment of novel embryonic stem cell lines derived from the common marmoset (Callithrix jacchus)
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DOI：
10.1634/stemcells.2004-0366
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发表时间：
2005-10-01
期刊：
影响因子：
5.2
通讯作者：
Tani, K
中科院分区：
文献类型：
--
作者：
Sasaki, E;Hanazawa, K;Tani, K
人类胚胎干细胞（hESC）系的成功建立，通过促进分化的ESCs移植到特定器官，开创了再生医学的新纪元。然而，hESC体内治疗的安全性和有效性问题仍有待解决。使用动物模型系统（包括非人类灵长类动物）进行的临床前研究对于评估 IIESC 疗法的安全性和有效性至关重要。此前，我们证明普通狨猴是适合造血干细胞疗法临床前研究的实验动物模型。由于该动物模型也适用于 ESC 疗法的临床前试验，因此我们建立了新型普通狨猴 ESC (CMESC) 系。为了获得狨猴胚胎，我们开发了一种新的胚胎收集系统，每三周可以从每对狨猴中获得囊胚。通过免疫手术分离内细胞团并铺在小鼠胚胎饲养层上。部分CMESC系连续培养超过1年。这些 CMESC 系显示碱性磷酸酶活性并表达阶段特异性胚胎抗原 (SSEA)-3、SSEA-4、TRA-1-60 和 TRA-1-81。另一方面，没有检测到SSEA-1。此外，我们的新型 CMESC 是多能的，免疫缺陷小鼠体内畸胎瘤形成和体外分化实验证明了这一点。我们建立的 CMESC 系和普通狨猴为了解分化机制以及开发使用 hESC 的再生疗法提供了出色的实验模型系统。
The successful establishment of human embryonic stem cell (hESC) lines has inaugurated a new era in regenerative medicine by facilitating the transplantation of differentiated ESCs to specific organs. However, problems with the safety and efficacy of hESC therapy in vivo remain to be resolved. Preclinical studies using animal model systems, including nonhuman primates, are essential to evaluate the safety and efficacy of IIESC therapies. Previously, we demonstrated that common marmosets are suitable laboratory animal models for preclinical studies of hematopoietic stern cell therapies. As this animal model is also applicable to preclinical trials of ESC therapies, we have established novel common marmoset ESC (CMESC) lines. To obtain marmoset embryos, we developed a new embryo collection system, in which blastocysts can be obtained every 3 weeks from each marmoset pair. The inner cell mass was isolated by immunosurgery and plated on a mouse embryonic feeder layer. Some of the CMESC lines were cultured continuously for more than 1 year. These CMESC lines showed alkaline phosphatase activity and expressed stage-specific embryonic antigen (SSEA)-3, SSEA-4, TRA-1-60, and TRA-1-81. On the other hand, SSEA-1 was not detected. Furthermore, our novel CMESCs are pluripotent, as evidenced by in vivo teratoma formation in immunodeficient mice and in vitro differentiation experiments. Our established CMESC lines and the common marmoset provide an excellent experimental model system for understanding differentiation mechanisms, as well as the development of regenerative therapies using hESCs.