Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential
Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential
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DOI：
10.1242/jcs.01103
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发表时间：
2004-06-15
影响因子：
4
通讯作者：
Schiller, PC
中科院分区：
文献类型：
--
作者：
D'Ippolito, G;Diabira, S;Schiller, PC
我们在这里报告的非转化的多能人类细胞从骨髓中分离后，一个独特的扩展/选择程序的人口。该程序旨在提供类似于体内微环境的条件，该微环境是最原始干细胞的家园。在低氧张力下，将骨髓粘附细胞和非粘附细胞在纤连蛋白上共培养14天。分离小贴壁细胞集落，并在低密度、低氧张力和2%胎牛血清下在纤连蛋白上进一步扩增。它们表达高水平的CD 29、CD 63、CD 81、CD 122、CD 164、肝细胞生长因子受体（cMet）、骨形态发生蛋白受体1B（BMPR 1B）和神经营养酪氨酸激酶受体3（NTRK 3），并且对CD 34、CD 36、CD 45、CD 117（cKit）和HLA-DR呈阴性。和端粒酶在所有检测的培养物中表达。细胞倍增时间为36至72小时，并且细胞已在培养物中扩增超过50个群体倍增。这群细胞一直从3岁至72岁的男性和女性中分离出来。细胞集落表达了胚胎干细胞以及中胚层、内胚层和外胚层来源的谱系中发现的许多标记物。它们已经分化成骨形成成骨细胞、软骨形成软骨细胞、脂肪形成脂肪细胞和神经细胞，以及表达与胰岛相关基因的附着非依赖性球形簇。基于其独特的特征和性质，我们将其称为人骨髓分离的成体多谱系诱导细胞或迈阿密细胞。迈阿密细胞广泛增殖而没有衰老或丧失分化潜能的证据，因此可能代表遗传性或退行性疾病的细胞疗法的理想候选者。
We report here the isolation of a population of non-transformed pluripotent human cells from bone marrow after a unique expansion/selection procedure. This procedure was designed to provide conditions resembling the in vivo microenvironment that is home for the most-primitive stem cells. Marrow-adherent and -nonadherent cells were co-cultured on fibronectin, at low oxygen tension, for 14 days. Colonies of small adherent cells were isolated and further expanded on fibronectin at low density, low oxygen tension with 2% fetal bovine serum. They expressed high levels of CD29, CD63, CD81, CD122, CD164, hepatocyte growth factor receptor (cMet), bone morphogenetic protein receptor 1B (BMPR1B), and neurotrophic tyrosine kinase receptor 3 (NTRK3) and were negative for CD34, CD36, CD45, CD117 (cKit) and HLA-DR. The embryonic stem cell markers Oct-4 and Rex-1, and telomerase were expressed in ail cultures examined. Cell-doubling time was 36 to 72 hours, and cells have been expanded in culture for more than 50 population doublings. This population of cells was consistently isolated from men and women of ages ranging from 3- to 72-years old. Colonies of cells expressed numerous markers found among embryonic stem cells as well as mesodermal-, endodermal- and ectodermal-derived lineages. They have been differentiated to bone-forming osteoblasts, cartilage-forming chondrocytes, fat-forming adipocytes and neural cells and to attachment-independent spherical clusters expressing genes associated with pancreatic islets. Based on their unique characteristics and properties, we refer to them as human marrow-isolated adult multilineage inducible cells, or MIAMI cells. MIAMI cells proliferate extensively without evidence of senescence or loss of differentiation potential and thus may represent an ideal candidate for cellular therapies of inherited or degenerative diseases.