Common Muscle, Hematopoietic and Neural Stem Cells

描述（由申请人提供）： 具有转分化能力的多能干细胞（PSC0）， 在治疗大量恶性肿瘤中具有显著的潜在效用， 和非恶性疾病。 虽然干细胞的命运一直是 被认为是不可逆转的，注定要局限在一个 组织类型、干细胞分化的可塑性和适应性 根据不同的微环境线索， 最近记录的。 干细胞可塑性的程度显示， 胚胎和成人PSC和相对容易与干细胞已经 指示分化成不同原始胚层组织 起源承诺新的和令人兴奋的细胞疗法的途径。 然而目前， 我们仍然不知道所描述的PSC的真实身份， 不知道通用干细胞是否可以在不同的 胎儿和成人组织。 为了更好地理解和评估 PSC并研究如何操纵它们的分化程序， 将研究三个具体目标。 首先，我们假设一种常见的罕见的 具有多种组织分化潜能的PSC群体可以 在骨骼肌、骨髓和脑组织中发现， 能够转分化为功能性肌源性、造血性和 神经元细胞 其次，我们将研究这些干细胞是否有能力， 通过在一个地点自我更新分裂和迁移到另一个地点， 多能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的干细胞的命运是否可以 在体外进行调节，并测试是否响应于不同的外源刺激， 分化成一种组织类型可能比其他分化更有利 途径。 本申请中提出的研究对4种主要的 本申请书中确定的研究需求。 只是检查 影响这些细胞可塑性的参数，如多能性， 分化、克隆性、归巢和对其命运的体外操纵， 是否有可能将PSC研究领域推向临床 相关性和治疗适用性。

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.