A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.

A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.
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DOI:
10.1084/jem.20040440
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发表时间:
2004-07-19
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Wernet P
Wernet P
中科院分区:
其他
文献类型:
--
作者:
Kögler G;Sensken S;Airey JA;Trapp T;Müschen M;Feldhahn N;Liedtke S;Sorg RV;Fischer J;Rosenbaum C;Greschat S;Knipper A;Bender J;Degistirici O;Gao J;Caplan AI;Colletti EJ;Almeida-Porada G;Müller HW;Zanjani E;Wernet P

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这里描述了一种来自人类脐带血的新的、本质上多能的、CD45阴性的细胞群,称为非限制性成体干细胞(USSC)。这种稀有细胞群可以贴壁生长,可以扩增至 1015 个细胞而不丧失多能性。体外 USSCs 显示出同质分化为成骨细胞、成软骨细胞、脂肪细胞、造血细胞和神经细胞,包括表达神经丝、钠通道蛋白和各种神经递质表型的星形胶质细胞和神经元。将 USSC 立体定向植入完整的成年大鼠大脑中,结果显示人类 Tau 阳性细胞持续存在长达 3 个月,并表现出迁移活性和典型的神经元样形态。在动物模型中证实了 USSC 沿中胚层和内胚层途径的体内分化。将负载 USSC 的磷酸钙圆柱体移植到裸鼠股骨后观察到骨重建。将载有细胞的明胶海绵移植到裸鼠体内后发生软骨形成。将 USSC 移植到非损伤模型(免疫前的胎羊)中,可实现高达 5% 的人类造血移植。 USSC 移植数月后,在绵羊心脏的心房和心室中检测到超过 20% 的产生白蛋白的人实质肝细胞,且不存在细胞融合,并且在羊心脏的心房和心室中检测到大量的人心肌细胞。在这些动物中均未观察到肿瘤形成。
Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 1015 cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals.
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