Application of nuclear transferred embryonic stem cells for reconstitution of hematopoiesis

核移植胚胎干细胞在造血重建中的应用

• 批准号: 17591020
• 负责人: NAKAMURA Yukio
• 金额: $ 2.24万
• 依托单位: Cell Engineering Division, RIKEN BioResource Center (RIKEN BRC)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591020/
• 关键词: Embryonic stem cell; Nuclear transfer; Hematopoiesis; Bone marrow transplantation; Hematopoietic stem cell

The establishment of a number of human embryonic stem (ES) cell lines has spurred research into the potential applications of such cells. The use of ES cell-derived cell populations for cell therapy appears to be one of the more promising clinical applications. However, there are a few reasons to limit clinical uses of the cells derived from ES cells. One is in the case of a mismatch of major histo-compatibility (MHC) antigen between the ES cells and the recipient's cells. This limitation may be overcome in several ways: an induction of tolerance in the recipient using ES cell-derived antigen-presenting cells; production of many ES cell lines to cover many types of MHC; production of cloned ES cell lines that possess nuclei derived from the recipient, i.e. so called "therapeutic cloning".The establishment of nuclear transferred ES (ntES) cell line is possible with mouse oocytes and nuclei. On the other hand, although the establishment of human ntES cell line has not been succeeded yet, … More it is highly likely that the technology to establish human ntES cell line will be developed in the future. Prior to the use of human ntES cell lines in the clinic, many basic researches should be performed using mouse and/or primate ntES cell lines.Since many groups have already reported that hematopoietic cells can be derived from human ES cells, hematopoietic cells may be also derived from human ntES cells. Then, we have tested whether hematopoietic cells can be derived from mouse ntES cells. First, we have analyzed the characteristics of several mouse ntES cell lines. All mouse ntES cell lines tested have demonstrated that they have the characteristics quite similar to ordinary ES cell lines, e.g., in morphology, cell surface phenotype, and gene expression pattern. Next, we have tested whether mouse ntES cells could produce hematopoietic cells following the induction of those cells into hematopoietic cells. As the results, all mouse ntES cell lines tested could produce hematopoietic cells robustly.We are currently studying whether hematopoietic stem cells are included in the hematopoietic cell population produced from mouse ntES cells. In addition, we will test the potential of those hematopoietic stem cells whether they can reconstitute hematopoietic cells in vivo by transplantation assay. Less

许多人胚胎干细胞系的建立促进了对这些细胞潜在应用的研究。使用ES细胞衍生的细胞群进行细胞治疗似乎是更有前途的临床应用之一。然而，存在限制来自ES细胞的细胞的临床应用的一些原因。一种是在ES细胞和受体细胞之间的主要组织相容性（MHC）抗原错配的情况下。这种限制可以通过几种方式克服：使用ES细胞衍生的抗原呈递细胞在受体中诱导耐受;产生许多ES细胞系以覆盖许多类型的MHC;产生具有来自受体的核的克隆ES细胞系，即所谓的“治疗性克隆”。另一方面，虽然人ntES细胞系的建立尚未成功， ...更多信息 建立人ntES细胞系的技术很可能在未来得到发展。在将人ntES细胞系应用于临床之前，需要对小鼠和/或灵长类动物的ntES细胞系进行大量的基础研究，由于已有多个研究组报道造血细胞可以来源于人ES细胞，因此造血细胞也可以来源于人ntES细胞。然后，我们测试了造血细胞是否可以从小鼠ntES细胞中衍生。首先，我们分析了几种小鼠ntES细胞系的特性。所有测试的小鼠ntES细胞系都证明它们具有与普通ES细胞系非常相似的特性，例如，形态学、细胞表面表型和基因表达模式。接下来，我们测试了小鼠ntES细胞在将这些细胞诱导成造血细胞后是否可以产生造血细胞。结果显示，所有的小鼠ntES细胞株都能稳定地产生造血细胞。我们正在研究小鼠ntES细胞产生的造血细胞群中是否包含造血干细胞。此外，我们将通过移植试验来测试这些造血干细胞是否能够在体内重建造血细胞。少

项目成果

Refinement of cytokine use in the in vitro expansion of erythroid cells.

细化红细胞体外扩增中细胞因子的使用。

• 发表时间: 2006
• 期刊: Human Cell 19
• 作者: Miharada;K.;Hiroyama;T.;Sudo;K.;Nagasawa;T.;Nakamura;Y.
• 通讯作者: Y.

Mesenchymal progenitors able to differentiate into osteogenic, chondrogenic, and/or adipogenic cells in vitro are present in most primary fibroblast-like cell populations

• DOI: 10.1634/stemcells.2006-0504
• 发表时间: 2007-07-01
• 期刊: STEM CELLS
• 影响因子: 5.2
• 作者: Sudo, Kazuhiro;Kanno, Megunh;Nakamura, Yukio
• 通讯作者: Nakamura, Yukio

Long-lasting in vitro hematopoiesis derived from primate embryonic stem cells

• DOI: 10.1016/j.exphem.2006.03.004
• 发表时间: 2006-06-01
• 期刊: EXPERIMENTAL HEMATOLOGY
• 影响因子: 2.6
• 作者: Hiroyama, Takashi;Miharada, Kenichi;Nakamura, Yukio
• 通讯作者: Nakamura, Yukio

Essential role for gene profiling analysis in the authentication of human cell lines

• DOI: 10.1111/j.1749-0774.2005.00007.x
• 发表时间: 2006-02
• 期刊: Human Cell
• 影响因子: 4.3
• 作者: Kaori Yoshino;Emi Iimura;K. Saijo;S. Iwase;K. Fukami;T. Ohno;Y. Obata;Yukio Nakamura