Yoshida Shuro, Ishikawa Fumihiko, Kawano Noriaki, Shimoda Kazuya, Nagafuchi Seiho, Shimoda Shinji, Yasukawa Masaki, Kanemaru Takaaki, Ishibashi Hiromi, Shultz Leonard D, Harada Mine
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Stem Cells. 2005 Oct;23(9):1409-16. doi: 10.1634/stemcells.2005-0079.
Here we report the capacity of human cord blood (CB)-derived cells to generate insulin-producing cells. To investigate in vivo capacity of human CB-derived cells, T cell-depleted mononuclear cells were intravenously transplanted into nonobese diabetic/severe combined immunodeficient/beta2-microglobulinnull mice within 48 hours of birth. At 1-2 months post-transplantation, immunofluorescence staining for insulin and fluorescence in situ hybridization (FISH) analysis using a human chromosome probe indicated that human CB-derived cells generated insulin-producing cells at a frequency of 0.65%+/-0.64% in xenogeneic hosts. Reverse transcription-polymerase chain reaction analysis confirmed the transcription of human insulin in the pancreatic tissue of the recipient mice. To clarify the mechanism underlying CB-derived insulin-producing cells, double FISH analysis using species-specific probes was performed. Almost equal proportions of human chromosome+ murine chromosome- insulin+ cells and human chromosome+ murine chromosome+ insulin+ cells were present in recipient pancreatic islets. Taken together, human CB contains progenitor cells, which can generate insulin-producing cells in recipient pancreatic tissues across a xenogeneic histocompatibility barrier by fusion-dependent and -independent mechanisms.
在此,我们报告了人脐带血(CB)来源的细胞生成胰岛素分泌细胞的能力。为了研究人CB来源细胞的体内能力,在出生后48小时内,将去除T细胞的单核细胞静脉注射到非肥胖糖尿病/重症联合免疫缺陷/β2-微球蛋白缺失小鼠体内。移植后1 - 2个月,使用人染色体探针进行胰岛素免疫荧光染色和荧光原位杂交(FISH)分析表明,在异种宿主中,人CB来源的细胞以0.65%±0.64%的频率生成胰岛素分泌细胞。逆转录-聚合酶链反应分析证实了受体小鼠胰腺组织中人胰岛素的转录。为了阐明CB来源的胰岛素分泌细胞的潜在机制,使用物种特异性探针进行了双重FISH分析。在受体胰岛中,人染色体+鼠染色体-胰岛素+细胞和人染色体+鼠染色体+胰岛素+细胞的比例几乎相等。综上所述,人CB含有祖细胞,其可通过融合依赖和非依赖机制跨越异种组织相容性屏障在受体胰腺组织中生成胰岛素分泌细胞。