MInnesota Human MAPC Training Grant

描述(由申请人提供)： 我们在人、小鼠和大鼠的骨髓中发现了一种罕见的祖细胞，我们称之为多能成体祖细胞或MAPC。MAPC增殖而不衰老，单个MAPC可分化为大多数中胚层细胞类型、神经外胚层样细胞和肝细胞样细胞。MAPC在免疫缺陷小鼠体内输注时不会形成肿瘤，但会根据局部提示分化为造血细胞和肺、肠、肝的上皮细胞。当注射到囊胚中时，单个MAPC对嵌合动物的所有组织都有贡献。MAPC也可能具有向胰腺内分泌细胞分化的能力。 我们可以常规地从60%的正常人骨髓中分离MAPC，以及从C57B16和129小鼠的骨髓中分离MAPC，维持MAPC的多能性需要细胞保持严格控制的密度。我们的经验是，学习MAPC培养技术的新研究人员通常需要几周的实践经验来衡量细胞应该保持的密度和细胞传代的时间。由于基于MAPC的疗法的发展，如β细胞的衍生，将需要大量的研究人员能够获得MAPC并获得MAPC培养技术的知识，我们建议为NIH资助的研究人员建立一个培训计划，目的是传播人类和啮齿动物MAPC以及人类和啮齿动物MAPC培养技术。为了实现这一目标，我们建议在明尼苏达大学对研究人员进行为期4-6周的MAPC培养技术培训。研究人员将接受从新鲜人、小鼠和/或大鼠骨髓中选择MAPC，维持已建立的MAPC细胞系，以及MAPC分化为中胚层、内胚层和神经外胚层细胞类型的培训。需要资金支持一名技术员以及建立、维护和区分MAPC的用品，以便一次培训2名调查人员，为期4-6周。

DESCRIPTION (provided by applicant): We identified a rare progenitor cell in BM of humans, mice and rats, which we have termed Multipotent Adult Progenitor Cell or MAPC. MAPC proliferate without senescence and single MAPC differentiate into most mesodermal cell types, neuroectoderm-like and hepatocyte-like cells. MAPC do not form tumors when infused in immunodeficient mice, but differentiate in response to local cues into hematopoietic cells and epithelium of lung, intestine and liver. When injected in the blastocyst, single MAPC contribute to all tissues of the chimeric animal. MAPC may also be capable of differentiation to pancreatic endocrine cells. We can routinely isolate MAPC from >60% of normal human BMs, as well from BMs from C57B16 and 129 mice, maintaining MAPC pluripotent requires that cells are maintained at tightly controlled densities. It is our experience that new investigators learning MAPC culture techniques commonly require several weeks of hands-on experience to gauge the density at which cells should be maintained and the time of cell passaging. As the development of MAPC-based therapies, such as derivation of beta cells, will require that a large number of investigators have access to MAPC and gain knowledge of MAPC culture techniques, we propose to establish a training program for NIH-funded investigators with as goal to disseminate human as well as rodent MAPC, and human and rodent MAPC culture technology. To achieve this goal, we propose to accommodate training of investigators in MAPC culture techniques for a 4-6 week period at the University of Minnesota. Investigators will be trained in the selection of MAPC from fresh human, mouse and / or rat bone marrow, maintenance of established MAPC cell lines, and differentiation of MAPC towards mesodermal, endodermal and neuroectodermal cell types. Funding is requested for support of a technician as well as supplies to establish, maintain and differentiate MAPC, to train 2 investigators for 4-6 weeks at a time.