Melanocyte Stem Cells in Regenerative Medicine

再生医学中的黑素细胞干细胞

• 批准号: 9017807
• 负责人: THOMAS J HORNYAK
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9017807
• 关键词: Acute; Biochemical; Biochemistry; CD34 gene; Caring; Cell surface; Cells; Chronic; Coupled; Data; Dermal; Development; Disease; Epithelial; Epithelial Cells; Exhibits; Fluorescence-Activated Cell Sorting; Gene Expression Profiling; Gene Proteins; Generations; Genetic; Germ; Goals; Hair; Hair follicle structure; Healthcare; Human; In Vitro; Laboratories; Laboratory Research; Maryland; Methods; Molecular; Molecular Biology; Mus; Natural regeneration; Nerve; Nerve Regeneration; Nervous System Trauma; Nervous system structure; Neural Crest; Neural Crest Cell; Neurodegenerative Disorders; Neuroglia; Neurons; P-Cadherin; Pathway interactions; Pigments; Population; Property; Proteins; Recovery; Regenerative Medicine; Research; Resources; Rest; Secondary to; Signal Pathway; Site; Skin; Stem cells; Structure; Supporting Cell; System; Tetanus Helper Peptide; Tissues; Transgenic Mice; Transgenic Organisms; Traumatic Nerve Injury; Universities; Veterans; analog; base; burden of illness; cell type; design; human stem cells; in vivo; injured; keratinocyte; medical schools; melanocyte; mouse model; precursor cell; progenitor; protein biomarkers; public health relevance; regenerative; research study; selective expression; stem cell population; tongue papilla

DESCRIPTION (provided by applicant): The proposed study is designed to determine how distinct subsets of melanocyte stem cells (MSCs) we have identified are regulated and maintained in the stem cell state and contribute to neural crest-derived cell regeneration. The rationale for the study is based upon our discovery that MSCs not only populate a region of the murine hair follicle (HF) termed the bulge, also the site of keratinocyte stem cells (KcSCs) of the HF, but also the secondary hair germ (SHG), a transient structure at the base of the telogen, or resting, HF adjacent to the dermal papilla. Our laboratory has developed methods to separate and study these two cell subsets in the viable state using a combination of a unique transgenic mouse system and fluorescence-activated cell sorting (FACS).The objectives of our studies are to discover specific markers of these stem cell subsets and to determine whether CD34+ MSCs in mice, and their cellular analogs in humans, can regenerate functional glial and neuronal cells, as suggested by preliminary data. We will also determine both in vitro and in vivo whether the CD34+ MSC subset, which exhibits an expanded developmental potential compared to CD34- MSCs, can regenerate neural crest- derived glial and neuronal cells. Information obtained from murine experiments will be used to identify comparable stem cell populations from human skin. These studies will be accomplished a unique, bitransgenic mouse line we have developed, Dct-H2BGFPki, in combination with the FACS facility and other core resources associated with my research laboratory located in the Department of Biochemistry and Molecular Biology at the University of Maryland School of Medicine. The results of these studies should have a positive impact on the health care of Veterans. Our discovery that the CD34+ MSC subset selectively expresses glial and neuronal markers may provide a strategy for using cells easily obtained from human skin to be used to support Veteran recovery from neurological injury and neurodegenerative disease.

描述（由申请人提供）： 这项拟议的研究旨在确定我们已经确定的黑素细胞干细胞（MSC）的不同子集如何在干细胞状态下受到调节和维持，并有助于神经嵴源性细胞再生。该研究的基本原理是基于我们的发现，即MSC不仅填充称为隆突的鼠毛囊（HF）的区域，也填充HF的角质形成细胞干细胞（KcSC）的部位，而且还填充次级毛胚（SHG），其是在休止期基部的瞬时结构，或邻近真皮乳头的静止HF。我们的实验室已经开发了分离和研究这两种细胞亚群的方法，使用独特的转基因小鼠系统和荧光激活细胞分选（FACS）的组合。我们的研究的目的是发现这些干细胞亚群的特异性标志物，并确定小鼠中的CD 34 + MSC及其在人类中的细胞类似物是否可以再生功能性胶质细胞和神经元细胞，正如初步数据所显示的那样。我们还将在体外和体内确定与CD 34-MSC相比表现出扩展的发育潜力的CD 34 + MSC亚群是否可以再生神经嵴衍生的胶质细胞和神经元细胞。从鼠实验中获得的信息将用于鉴定来自人皮肤的可比干细胞群。这些研究将通过我们开发的独特的双转基因小鼠系Dct-H2 BGFPki，结合位于马里兰州医学院生物化学和分子生物学系的我的研究实验室的FACS设施和其他核心资源来完成。这些研究的结果应该对退伍军人的医疗保健产生积极的影响。我们发现CD 34 + MSC亚群选择性表达神经胶质和神经元标记物，这可能为使用容易从人皮肤获得的细胞来支持退伍军人从神经损伤和神经退行性疾病中恢复提供策略。