Therapeutic hair follicle-derived neurospheres

治疗性毛囊源性神经球

基本信息

批准号：
6934274
负责人：
MENG YANG
金额：
$ 14.98万
依托单位：
ANTICANCER, INC.
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-15 至 2006-04-14
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The ready availability of pluripotent adult stem cells would have many important therapeutic applications. Our recent results suggest that the hair follicle is a promising source for such stem cells. Our recent discovery that the neural stem cell marker, nestin is expressed in hair-follicle stem cells (Li, L., et al. Nestin expression in hair follicle sheath progenitor cells. Proc. Natl. Acad. Sci. USA 100, 9658-9662, 2003) suggested that hair-follicle stem cells and neural stem cells have common features. Recently, we have demonstrated that the hair follicle gives rise to blood vessels in vivo with the blood vessels apparently originating from the hair-follicle stem cells (Amoh, Y., et al. Nascent blood vessels in the skin arise from nestin-expressing hair follicle cells. Proc. Natl. Acad. Sci. USA, in press). In preliminary experiments, we have demonstrated in vitro that hair-follicle stem cells can be induced to form neurospheres, which in turn form neurons (Amoh, Y., Li, L., and Hoffman, R.M., unpublished results). These results suggest pluripotent hair follicle adult stem cells could have important therapeutic applications, in particular for neurological diseases. This application utilizes transgenic mice with green fluorescent protein (GFP) under the control of the nestin regulatory sequences as the source of labeled hair follicle cells. In the nestin-GFP transgenic mice, nestin-expressing hair-follicle stem cells are located in the permanent upper hair follicle right below the sebaceous glands and above the errector pili muscle in the follicle bulge area. This group of nestin-expressing cells in the bulge area of the follicle can be activated by anagen induction and form the new hair follicles as well as a blood-vessel network. Immunohistochemical staining revealed that the nestin-GFP-expressing cells in the hair follicle bulge co-express nestin, GFP, and keratin-15 one of the markers of hair-follicle stem cells. The blood vessels formed from the follicle co-express CD-31 an endothelial cell marker as well as GFP. We have shown that the isolated hair-follicle nestin-expressing cells can form neurospheres in vitro that can be switched to form either neurons or blood vessels. The specific aims of this application are as follows: (1) Optimization of isolation of nestin-GFP-expressing hair-follicle stem cells for neurosphere conversion; (2) Determination of the optimal conditions of hairfollicle- stem-cell-derived neurospheres to form neurons. In Phase II, we will use optimized hair follicle derived neorospheres developed in Phase I to determine their therapeutic efficiency to produce neurons, blood vessels, and hair follicles in vivo. Human hair-follicle stem cells will also be developed for therapeutic potential in Phase II.

描述（由申请人提供）：多能成体干细胞的现成可用性将具有许多重要的治疗应用。我们最近的研究结果表明，毛囊是此类干细胞的一个有前途的来源。我们最近发现，神经干细胞标记物巢蛋白在毛囊干细胞中表达（Li, L., et al. 毛囊鞘祖细胞中的巢蛋白表达。Proc. Natl. Acad. Sci. USA 100, 9658- 9662, 2003）表明毛囊干细胞和神经干细胞具有共同特征。最近，我们已经证明毛囊在体内产生血管，这些血管显然源自毛囊干细胞（Amoh，Y.等人。皮肤中的新生血管源自表达巢蛋白的毛发）滤泡细胞。美国国家科学院，出版中）。在初步实验中，我们已经在体外证明毛囊干细胞可以被诱导形成神经球，神经球进而形成神经元（Amoh，Y.，Li，L.和Hoffman，R.M.，未发表的结果）。这些结果表明多能毛囊成体干细胞可能具有重要的治疗应用，特别是对于神经系统疾病。该应用利用具有巢蛋白调控序列控制下的绿色荧光蛋白（GFP）的转基因小鼠作为标记毛囊细胞的来源。在巢蛋白-GFP转基因小鼠中，表达巢蛋白的毛囊干细胞位于皮脂腺正下方和毛囊隆起区域的竖毛肌上方的永久上毛囊中。毛囊凸起区域的这组表达巢蛋白的细胞可以通过毛发生长初期诱导激活，并形成新的毛囊和血管网络。免疫组织化学染色显示，毛囊凸起中表达巢蛋白-GFP的细胞共表达巢蛋白、GFP和角蛋白15（毛囊干细胞的标记物之一）。由毛囊形成的血管共表达 CD-31（一种内皮细胞标记）以及 GFP。我们已经证明，分离的毛囊巢蛋白表达细胞可以在体外形成神经球，神经球可以转变为神经元或血管。本申请的具体目的如下：（1）优化表达巢蛋白-GFP的毛囊干细胞用于神经球转化的分离； (2)确定毛囊干细胞来源的神经球形成神经元的最佳条件。在第二阶段，我们将使用第一阶段开发的优化的毛囊衍生的神经球来确定它们在体内产生神经元、血管和毛囊的治疗效率。人类毛囊干细胞也将在第二阶段开发用于治疗潜力。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chemotherapy targets the hair-follicle vascular network but not the stem cells.

化疗针对的是毛囊血管网络，而不是干细胞。

DOI：
发表时间：
2007-01
期刊：
影响因子：
0
作者：
Amoh, Yasuyuki;Li, Lingna;Katsuoka, Kensei;Hoffman, Robert M
通讯作者：
Hoffman, Robert M

Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells.

人毛囊多能干 (hfPS) 细胞促进周围神经损伤的再生：ES 和 iPS 细胞的有利替代品。

DOI：
发表时间：
2009-08-01
期刊：
影响因子：
4
作者：
Amoh, Yasuyuki;Kanoh, Maho;Niiyama, Shiro;Hamada, Yuko;Kawahara, Katsumasa;Sato, Yuichi;Hoffman, Robert M;Katsuoka, Kensei
通讯作者：
Katsuoka, Kensei

Multipotent hair follicle stem cells promote repair of spinal cord injury and recovery of walking function.

多能毛囊干细胞促进脊髓损伤的修复和行走功能的恢复。