Isolation and identification of tissue stem cell for clinical application

组织干细胞的分离鉴定及其临床应用

• 批准号: 17590350
• 负责人: OKANO Shinji
• 金额: $ 2.24万
• 依托单位: KYUSHU UNIVERCITY
• 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-17590350/
• 关键词: Tissue stem cell; Cord blood; I11 liver・liver regeneration; Vasculogenisis; FLK-1細胞; 肝組織再生; LDL受容体欠損マウス; 臍帯血液; 分化

Although tissue stem cells contribute to regeneration of tissue and has therapeutic potentials for clinical application of regenerative medicine, the use of the cells has some concerns including low proliferating capacity and low transplantable capacity as compared with ES cells. This study also reveals that ciliary body-derived tissue stem cells have an potential ability to differentiate into neural cells due to cell-aggregation without cell-proliferation. To overcome these issues, we identified and isolated a novel cell population, Albumin(ALB)+a-smooth muscle actin(a-SMA)VEGFR2+ cells, which also expressed the ES cell-expressing markers, and we also found out that the cells could differentiate to a-SMA+ smooth muscle cells or CD31+ vascular endothelial cells in the presence of PDGF-BB and VEGF, and could differentiate to ALB+ hepatocytes or CK18+ bile duct cells in the presence of HGF and EGF in vitro. Moreover, we found out that the non-stimulated VEGFR2+ cells could differentiate to α-SMA+ smooth muscle cells or CD31+ vascular endothelial cells, and HGF+EGF-stimulated VEGFR2+ cells could differentiate to hepatocytes or bile duct cells in vivo, when the cells were inoculated into subcapsule of spleens in partial hepatectomized adult mice.Furthermore, we identified and isolated a cord blood-derived cell population, CD45-CD133+CD34+VEGFR2+ cells, which could form colonies and differentiate to CD133-CD31+ vascular endothelial cells or α-SMA+ smooth muscle cells in the presence of VEGF, IGF, FGF-2,and/or PDGF-BB in vitro. In therapeutic cell transplantation for clinical setting, although there is a concern about rejection by sensitized allo-reactive memory T cells, the cord blood-derived CD45-VEGFR2+ cells has a potential source as endothelial progenitor cell (EPC), because we indicated that CCL2 was highly expressed in the ischemic muscular tissues using our murine limb ischemia models.

尽管组织干细胞有助于组织的再生，并具有再生医学临床应用的治疗潜力，但与ES细胞相比，组织干细胞的使用存在增殖能力低、可移植能力低等问题。本研究还揭示了睫状体来源的组织干细胞具有通过细胞聚集而不是细胞增殖而分化为神经细胞的潜在能力。为了克服这些问题，我们鉴定和分离了一种新的细胞群，白蛋白(ALB)+a-平滑肌肌动蛋白(a-SMA)VEGFR2+细胞，该细胞也表达ES细胞标志物，并发现在PDGF-BB和VEGF的存在下，该细胞可以分化为a-SMA+平滑肌细胞或CD31+血管内皮细胞，在HGF和EGF的作用下，该细胞在体外可以分化为ALB+肝细胞或CK18+胆管细胞。将未受刺激的VEGFR2+细胞接种于部分肝切除小鼠的脾被膜下，在体内可分化为α-SMA+血管内皮细胞或CD31+血管内皮细胞，经HGF+EGF刺激的VEGFR2+细胞在体内可分化为肝细胞或胆管细胞。在临床治疗性细胞移植中，尽管存在致敏的异反应记忆T细胞的排斥反应，但脐带血来源的CD45-VEGFR2+细胞具有作为内皮祖细胞(EPC)的潜在来源，因为我们使用我们的小鼠肢体缺血模型表明CCL2在缺血肌肉组织中高表达。

项目成果

Nonendothelial mesenchymal cell-derived MCP-1 is required for FGF-2-mediated therapeutic neovascularization - Critical role of the inflammatory/arteriogenic pathway

• DOI: 10.1161/01.atv.0000244684.23499.bf
• 发表时间: 2006-11-01
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Fujii, Takaaki;Yonemitsu, Yoshikazu;Sueishi, Katsuo
• 通讯作者: Sueishi, Katsuo

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephrophathic metabolic syndrome in severe hind limb ischemia

自由基清除剂而非 FGF-2 介导的血管生成疗法可挽救严重后肢缺血的肌肾代谢综合征

• 发表时间: 2006
• 期刊: Am J Physiol Heart Circ Physiol 290
• 作者: Kaneko K;et al.
• 通讯作者: et al.

Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation

• DOI: 10.1016/j.brainres.2006.03.093
• 发表时间: 2006-06-06
• 期刊: BRAIN RESEARCH
• 影响因子: 2.9
• 作者: Kohno, Ri-ichiro;Ikeda, Yasuhiro;Sueishi, Katsuo
• 通讯作者: Sueishi, Katsuo

Critical roles of memory T cells and atidonor immunoglobulin in rejection of allogeneic marrow cells in sensitized recipient mice.

记忆 T 细胞和供体免疫球蛋白在致敏受体小鼠同种异体骨髓细胞排斥中的关键作用。

• 发表时间: 2006
• 期刊: Transplantation 82
• 作者: Yamao K;Sawaki A;Mizuno N;Shimizu Y;Yatabe Y;Koshikawa T;C.J.Kim et al.;Nagata S et al.
• 通讯作者: Nagata S et al.

Nonendothelial mesenchymal cell-derived MCP-1 is required for FGF-2-mediated therapeutic neovascularization : critical role of the inflammatory/artheriogenic pathway.

FGF-2 介导的治疗性新血管形成需要非内皮间充质细胞衍生的 MCP-1：炎症/动脉粥样硬化途径的关键作用。

• 发表时间: 2006
• 期刊: Arterioscler Thromb Vasc Biol. 26
• 作者: Yatabe Y;Kosaka T;Takahashi T;Mitsudomi T;Fujii T et al.
• 通讯作者: Fujii T et al.