Lengerke Claudia, Kim Kitai, Lerou Paul, Daley George Q
Division of Pediatric Hematology/Oncology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.
Ann N Y Acad Sci. 2007 Jun;1106:209-18. doi: 10.1196/annals.1392.011. Epub 2007 Mar 14.
Embryonic stem cells (ESCs) hold unique promise for the development of cell replacement therapies, but derivation of therapeutic products from ESCs is hampered by immunological barriers. Creation of HLA-typed ESC banks, or derivation of customized ESC lines by somatic cell nuclear transfer, have been envisioned for engineering histocompatible ESC-derived products. Proof of principle experiments in the mouse have demonstrated that autologous ESCs can be obtained via nuclear transfer and differentiated into transplantable tissues, yet nuclear transfer remains a technology with low efficiency. Parthenogenesis provides an additional means for deriving ESC lines. In parthenogenesis, artificial oocyte activation initiates development without sperm contribution and no viable offspring are produced in the absence of paternal gene expression. Development proceeds readily to the blastocyst stage, from which parthenogenetic ESC (pESC) lines can be derived with high efficiency. We have recently shown that when pESC lines are derived from hybrid mice, early recombination events produce heterozygosity at the major histocompatibility complex (MHC) loci in some of these lines, enabling the generation of histocompatible differentiated cells that can engraft immunocompetent MHC-matched mouse recipients. Here, we explore the differentiation potential of murine pESCs derived in our laboratory.
胚胎干细胞（ESCs）在细胞替代疗法的发展中具有独特的前景，但从ESCs中获取治疗产品受到免疫屏障的阻碍。人们设想建立HLA分型的ESC库，或通过体细胞核移植获得定制的ESC系，以制造组织相容性的ESC衍生产品。小鼠的原理验证实验表明，自体ESCs可通过核移植获得并分化为可移植组织，但核移植仍然是一种效率较低的技术。孤雌生殖为获得ESC系提供了另一种方法。在孤雌生殖中，人工卵母细胞激活启动发育而无需精子参与，并且在没有父本基因表达的情况下不会产生存活后代。发育很容易进入囊胚阶段，从中可以高效地获得孤雌生殖ESC（pESC）系。我们最近发现，当从杂交小鼠中获得pESC系时，早期重组事件会在其中一些品系的主要组织相容性复合体（MHC）位点产生杂合性，从而能够生成可植入免疫活性MHC匹配小鼠受体的组织相容性分化细胞。在此，我们探索了我们实验室中获得的小鼠pESC的分化潜能。
