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Melanocyte Stem Cells in Regenerative Medicine

再生医学中的黑素细胞干细胞

基本信息

批准号：
10515349
负责人：
THOMAS J HORNYAK
金额：
--
依托单位：
BALTIMORE VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2024-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10515349
关键词：
Acute Animal Model Baltimore Brain CD34 gene Candidate Disease Gene Cell Separation Cell surface Cells Cerebral cortex Characteristics Chronic Clinical Demyelinating Diseases Demyelinations Dermis Differentiated Gene Disease Environment Exhibits Foundations Funding Gene Expression Genes Genomics Germ Glial Differentiation Goals Growth Hair Hair follicle structure Healthcare Human In Vitro Individual Knowledge Maryland Medical center Modeling Molecular Mus Myelin Basic Proteins Myelin Sheath Natural regeneration Nerve Nerve Regeneration Nervous System Trauma Neural Crest Neural Crest Cell Neural Retina Neurodegenerative Disorders Neurologic Effect Neurons Phase Phenotype Pigmentation physiologic function Procedures Property Proteins Regenerative Medicine Research Research Proposals Resting Phase Side Skin Source Spinal Ganglia Supporting Cell System Testing Therapeutic Therapeutic Uses Tissues Translating Universities Veterans Work base biomarker identification burden of illness cell type design genome-wide in vivo laboratory facility medical schools melanocyte nerve injury neural repair neurological recovery precursor cell protein biomarkers regeneration potential regenerative research and development stem cell population stem cells translational goal translational study

项目摘要

The proposed continuation study is designed to leverage information from our prior comprehensive characterization of subsets of hair follicle (HF) melanocyte stem cells (McSCs); to determine how a subset of skin-derived stem cells exhibiting the potential to myelinate neurons can be isolated from mammalian skin and utilized therapeutically. The rationale for the study is based upon our prior work demonstrating that CD34+ McSCs, located in the HF bulge, exhibit a neural crest stem cell phenotype and expression profile; and are not exclusively committed to melanocyte differentiation. By separating CD34+ McSCs from other cells in the murine HF and skin, we have been able to characterize the genome-wide expression profile and functional characteristics of CD34+ McSCs; which include their ability to form myelin sheaths surrounding neurons. By applying this information to identify other skin-derived stem cells with similar properties that can be isolated de novo; we believe that we can develop approaches to treat demyelinating disease and the effects of neurological trauma with highly-specific and selected skin-derived stem cells. The objectives of our studies are to: 1) apply specific markers of CD34+ McSCs to murine and human skin-derived stem cells with neural crest differentiation properties, or skin-derived precursors (SKPs), and 2) to identify specific subsets of SKPs with glial properties. An additional objective is to determine whether CD34+ McSCs, along with specific SKP subsets subsequently identified, support neural repair in an established neural injury model. These studies will be accomplished using individual and core laboratory facilities in both the Baltimore VA Medical Center and in the University of Maryland School of Medicine. The results of these studies should have a positive impact on the health care of Veterans. Our comprehensive genomic and functional characterization of CD34+ McSCs may enable a strategy for identifying a highly-specific stem cell population from human skin- useful for supporting Veteran recovery from neurological injury and neurodegenerative disease.

拟议的继续研究旨在利用我们先前的信息毛囊（HF）黑素细胞干细胞（McSC）亚群的综合表征; 以确定一组皮肤来源的干细胞如何表现出髓鞘形成的潜力，神经元可以从哺乳动物皮肤中分离并用于治疗。的理由这项研究是基于我们先前的工作，证明了位于HF隆突中的CD 34 + McSCs，表现出神经嵴干细胞表型和表达谱;并且不排他地致力于黑素细胞的分化。通过将CD 34 + McSCs与其他细胞分离，小鼠HF和皮肤，我们已经能够表征全基因组表达谱， CD 34 + McSCs的功能特征;包括它们形成髓鞘的能力周围的神经元通过应用这些信息来识别其他皮肤来源的干细胞，可以重新分离的类似性质;我们相信，我们可以开发方法，治疗脱髓鞘疾病和神经创伤的影响，选择皮肤来源的干细胞。我们的研究目的是：1）将CD 34 + McSCs的特异性标志物应用于小鼠和小鼠骨髓，具有神经嵴分化特性的人皮肤来源的干细胞，或皮肤来源的前体（SKPs），和2）鉴定具有神经胶质性质的SKPs的特定子集。一个另一个目的是确定CD 34 + McSCs，沿着特异性SKP亚群，随后鉴定，支持建立的神经损伤模型中的神经修复。这些研究将使用位于巴尔的摩的个人和核心实验室设施来完成 VA医学中心和马里兰州大学医学院。的结果予以研究应该对退伍军人的医疗保健产生积极的影响。我们全面 CD 34 + McSCs的基因组和功能表征可能有助于识别来自人类皮肤的高度特异性干细胞群-用于支持退伍军人康复神经损伤和神经退行性疾病。