Trounson Alan
Institute of Reproduction and Development, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia.
Reprod Biomed Online. 2002;4 Suppl 1:58-63. doi: 10.1016/s1472-6483(12)60013-3.
Pluripotential embryonic stem (ES) cells have been derived very efficiently from spare human embryos produced by IVF and grown in culture to the nascent blastocyst stage. The inner cell mass (ICM) is isolated by immunosurgery and grown on selected embryonic fibroblast monolayer cultures. ICM cells lose their memory for axis during formation of ES cell colonies and are then unable to integrate tissue formation with a body plan. ES cells form teratomas in vivo with cells and tissues representative of the three major embryonic lineages (ectoderm, mesoderm, endoderm). The ES cells are continuously renewable and can be directed to differentiate into early progenitors of neural stem cells (Noggin cells) and from there into mature neurons and glia (astrocytes and oligodendrocytes). The neural stem cells formed from human ES cells repopulate the brains of newborn mice when injected into the lateral cerebral ventricles, forming astrocytes dominantly in the parenchyma. The human neural cells can be observed migrating from the subventricular areas along the rostral migratory stream. Human neurons can be found in the olfactory bulb. Human ES cells can also be directed into cardiomyocytes when co-cultured with visceral endoderm-like cells (END-2). These observations provide further scope to explore stem cell therapies, gene therapies and drug discovery. For compatible transplantation, ES may need to be derived with a range of HLA types or by nuclear transplantation or stem cell fusion.
多能胚胎干细胞已非常高效地从体外受精产生的多余人类胚胎中获取,并在培养中生长至新生囊胚阶段。通过免疫手术分离内细胞团(ICM),并在选定的胚胎成纤维细胞单层培养物上培养。ICM细胞在形成胚胎干细胞集落的过程中失去了其轴向记忆,随后无法将组织形成与身体蓝图整合。胚胎干细胞在体内形成畸胎瘤,其中包含代表三个主要胚胎谱系(外胚层、中胚层、内胚层)的细胞和组织。胚胎干细胞可不断更新,并可被诱导分化为神经干细胞(诺金细胞)的早期祖细胞,进而分化为成熟的神经元和神经胶质细胞(星形胶质细胞和少突胶质细胞)。当将由人类胚胎干细胞形成的神经干细胞注射到新生小鼠的侧脑室时,它们会重新填充小鼠大脑,在脑实质中主要形成星形胶质细胞。可以观察到人类神经细胞从脑室下区域沿着吻侧迁移流迁移。在嗅球中可以发现人类神经元。当与内脏内胚层样细胞(END - 2)共培养时,人类胚胎干细胞也可被诱导分化为心肌细胞。这些观察结果为探索干细胞疗法、基因疗法和药物发现提供了更广阔的空间。为了实现兼容移植,可能需要通过一系列HLA类型、核移植或干细胞融合来获取胚胎干细胞。