Pluripotent Stem Cell using ES Cell Cytoplast

使用 ES 细胞质体的多能干细胞

• 批准号: 6458366
• 负责人: Naohiro Terada
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-15 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6458366
• 关键词: cell differentiation; cell fusion; chloramphenicol; cytoplasm; embryonic stem cell; genotype; green fluorescent proteins; laboratory mouse; leukemia inhibitory factor; pluripotent stem cells; tissue /cell culture; tissue /cell preparation

Self-renewing, totipotent embryonic stem (ES) cells may provide a virtually unlimited donor source for transplantation and tissue generation in vitro. Mouse ES cell-derived hematopoietic precursors, cardiomyocytes, neural precursors, or insulin-producing cells have been successful transplanted into recipient animals. Since human ES cells (and embyronic germ cells) were recently isolated and shown to have a similar potential for differentiation to mouse ES cells, ES-derived cells may be applied, in the near future, to patients with various diseases. Ultimately, in vitro-generated tissues from human ES cells may take the place, at least in part, or organ transplantation. ES-derived tissue specific cells may also be an ideal source for drug efficacy and toxicity testing. The promise of ES cell research is, however, tempered by the strong ethnical concerns regarding the use of fertilized human eggs to establish ES cells. In particular, in order to prepare human ES cells for large numbers of the histocompatibility types in population, there would be the necessity for a great increase in the use of human eggs. Here we attempt to generate pluripotent ES-like cells by fusion of adult somatic cells and the cytoplasts prepared from mouse ES cells. In our preliminary experiments, we have successfully generated pluripotent stem cells by ES cell-somatic cell fusion. Moreover, recent success in mammalian cloning indicates that the cytoplasm of fertilized eggs is sufficient to reprogram the somatic nuclei. The cytoplasm of ES cells may retain the ability to reprogram somatic nuclei as well. If the method could be applied to the human system, autologous pluripotent stem cells could be prepared for any individual using the one human ES line that has already been established. Pluripotent ES-like stem cells with the genotype of somatic cells could then be utilized for autologous cell replacement therapy and personal drug efficacy/toxicity test, inc combination with the in vitro differentiation techniques. In addition to such clinical significance, the current study could provide the basis for an improved system to explore the mechanisms underlying nuclear reprogramming.

自我更新，全能的胚胎茎（ES）细胞可能会提供几乎无限的供体来源，用于体外移植和组织产生。小鼠ES细胞衍生的造血前体，心肌细胞，神经前体或产生胰岛素的细胞已成功移植到受体动物中。由于最近分离出人类ES细胞（和雌激素细胞），并显示出与小鼠ES细胞分化相似的潜力，因此在不久的将来，可以将ES衍生的细胞应用于各种疾病的患者。最终，来自人类ES细胞的体外生成的组织至少部分或器官移植。 ES衍生的组织特异性细胞也可能是药物疗效和毒性测试的理想来源。然而，ES细胞研究的希望受到有关使用受精的人卵建立ES细胞的强烈种族问题。特别是，为了使人类ES细胞在人群中的大量组织相容性类型中制备，有必要大大增加人卵的使用。在这里，我们试图通过融合成年体细胞和由小鼠ES细胞制备的细胞体融合来产生多能ES样细胞。在我们的初步实验中，我们通过ES细胞性细胞融合成功地产生了多能干细胞。此外，最近在哺乳动物克隆方面的成功表明，受精卵的细胞质足以重新编程体细胞核。 ES细胞的细胞质也可以保留重新编程体细胞核的能力。如果该方法可以应用于人类系统，则可以使用已经建立的人类ES系列为任何个体准备自体多能干细胞。然后可以将具有体细胞基因型的多能ES样干细胞用于自体细胞替代疗法和个人药物疗效/毒性测试，INC与体外分化技术结合使用。除了这种临床意义外，当前的研究还可以为改进的系统探索核重编程的机制提供基础。