Common Muscle, Hematopoietic and Neural Stem Cells

常见的肌肉、造血和神经干细胞

• 批准号: 6436674
• 负责人: Edward F Srour
• 金额: $ 37.01万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6436674
• 关键词: cell differentiation; cell migration; cell population study; cell proliferation; flow cytometry; hematopoietic stem cells; laboratory mouse; muscle satellite cell; nerve stem cell; pluripotent stem cells; regeneration; southern blotting; stem cell transplantation; tissue /cell culture

DESCRIPTION (provided by applicant): Pluripotential stem cells (PSC0 with transdifferentiation capacity have a remarkable potential utility in the treatment of a large number of malignant and non-malignant diseases. Although the fate of stem cells has been considered irreversible and predestined to remain confined to within one tissue type, the plasticity and adaptability of stem cells to differentiate into multiple lineages in response to diverse microenvironmental cues has been recently documented. The degree of stem cell plasticity displayed by embryonic and adult PSC and the relative ease with which stem cells have been instructed to differentiate into tissues of different primordial germ layer origin promise new and exciting avenues for cellular therapy. Yet at present, we remain unaware of the true identity of PSC that have been described and ignorant as to whether a universal stem cell can be identified in different fetal and adult tissues. To better understand and evaluate the plasticity of PSC and to investigate how their differentiation programs can be manipulated, 3 specific aims will be examined. First, we hypothesize that a common rare population of PSC with multiple tissue differentiation potential can be identified in skeletal muscle, bone marrow and brain tissue and that all are capable of transdifferentiation into functional myogenic, hematopoietic and neuronal cells. Second, we will investigate if these stem cells are capable, through self-renewal division in one site and migration to another, of clonal pluripotential differentiation into specialized cells of different tissue types. Third, we will examine whether the fate of this common stem cell can be modulated in vitro and test if, in response to different exogenous stimuli, differentiation into one tissue type can be favored over other differentiation pathways. Studies proposed in this application are responsive to 4 of the primary research needs identified in this Request for Applications. Only be examining parameters that influence the plasticity of these cells such as pluripotential differentiation, clonality, homing and in vitro manipulation of their fate, would it be possible to forward the field of PSC research towards clinical relevance and therapeutic applicability.

描述(由申请人提供)： 具有转分化能力的多潜能干细胞(PSC0) 在治疗大量恶性肿瘤方面具有显著的潜在效用 和非恶性疾病。尽管干细胞的命运一直是 被认为是不可逆转的，注定要被限制在一个 组织类型、干细胞的可塑性和分化适应性 对不同的微环境线索作出反应的多个谱系 最近才被记录在案。干细胞可塑性程度通过以下方式显示 胚胎和成人的PSC以及干细胞相对容易地 指示分化为不同原始胚层的组织 Origin有望为细胞治疗开辟新的、令人兴奋的途径。然而目前， 我们仍然不知道PSC的真实身份，这些描述和 不知道通用干细胞是否可以在不同的 胎儿和成人组织。为了更好地了解和评估 PSC并调查他们的差异化计划如何被操纵， 将考察3个具体目标。首先，我们假设一种常见的稀有 具有多组织分化潜能的PSC群体可 在骨骼肌、骨髓和脑组织中被鉴定，而且都是 能够转分化为功能性的肌源性、造血性和 神经细胞。第二，我们将调查这些干细胞是否有能力， 通过在一个地点的自我更新分裂和向另一个地点的迁移，克隆 多向分化为不同组织的特化细胞 类型。第三，我们将研究这种常见干细胞的命运是否可以 在体外进行调节，并测试是否对不同的外源刺激做出反应， 分化成一种组织类型可能比其他分化更有利 小路。 本申请中提出的研究回应了4个小学 申请申请书中确定的研究需求。只是在检查 影响这些细胞可塑性的参数，如多潜能 分化、克隆、归宿和体外操纵它们的命运， 是否有可能将PSC的研究领域推向临床 相关性和治疗适用性。