Melanocyte Stem Cells in Regenerative Medicine

拟议的继续研究旨在利用我们之前的信息 毛囊(HF)黑素细胞干细胞(McSCs)亚群的综合表征 为了确定皮肤来源的干细胞亚群如何表现出髓鞘形成的潜力 神经元可以从哺乳动物的皮肤中分离出来，并用于治疗。该计划的基本原理 这项研究基于我们之前的工作，证明了位于HF凸起中的CD34 McSCs， 表现出神经脊干细胞的表型和表达谱； 致力于黑素细胞分化。通过将CD34 McSCs从体内其他细胞中分离出来 小鼠HF和皮肤，我们已经能够表征全基因组的表达谱和 CD34骨髓间充质干细胞的功能特性，包括其形成髓鞘的能力 周围的神经元。通过应用这些信息来鉴定其他皮肤来源的干细胞 可以从头开始隔离的类似属性；我们相信我们可以开发方法来 高特异度和特异度治疗脱髓鞘疾病及神经创伤的疗效观察 选定的皮肤来源的干细胞。 我们的研究目标是：1)将CD34-McSCs的特异性标记应用于小鼠和 具有神经脊分化特性的人皮肤来源的干细胞，或皮肤来源 前体(SKP)，以及2)识别具有神经胶质属性的SKP的特定子集。一个 另一个目标是确定CD34 McSCs和特定的SKP亚群 随后鉴定，支持神经修复中建立的神经损伤模型。这些 研究将使用巴尔的摩的个人和核心实验室设施来完成 弗吉尼亚医学中心和马里兰大学医学院。这些研究的结果 研究应该对退伍军人的医疗保健产生积极影响。我们全面的 CD34 McSCs的基因组和功能特征可能使识别 高度特异的人类皮肤干细胞群体--有助于支持退伍军人的康复 神经损伤和神经退行性疾病。

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.