Magrassi Lorenzo, Castello Sandra, Ciardelli Laura, Podesta Marina, Gasparoni Antonella, Conti Luciano, Pezzotta Stefano, Frassoni Francesco, Cattaneo Elena
Neurochirurgia Dipartimento di Chirurgia, Università di Pavia, IRCCS Policlinico S. 27100, Matteo, Pavia, Italy.
Mol Cell Neurosci. 2003 Feb;22(2):179-87. doi: 10.1016/s1044-7431(02)00029-5.
Earlier studies suggested that stem cells from one somatic tissue may generate differentiated elements of another, embryologically unrelated, tissue after an exchange in their positions through transplantation. Two reports indicated that murine and human neural stem cells of clonogenic origin after in vitro expansion in growth factor-supplemented media, may sustain hematopoiesis when injected into sublethally irradiated mice. Here we investigated if freshly dissociated fetal neural cells (fNC) share the reported hemopoietic potential of in vitro expanded neural cells. In order to minimize the risk of hemopoietic contamination, donor cells were taken from mouse E10.5 developing brains, before completion of blood vessel ingrowth into the brain; 10(6) fNC derived directly from fetal brains of transgenic mouse expressing an enhanced version of the green fluorescent protein were injected into the tail vein or directly into the bone marrow of sublethally irradiated (6 Gy) C57B16 mice. After transplantation, the presence of donor-derived cells was assessed at different survival times by FACS analysis, PCR, and clonogenic stem cell assays on peripheral blood and bone marrow. While bone marrow-derived cells were detected from 2 weeks onward after grafting, none of the mice grafted with neural embryonic cells demonstrated any sign of transdifferentiation into hemopoietic cells up to 16 months after transplantation. Our data indicate that ability to transdifferentiate from neural into the hematopoietic phenotype, if present, is acquired only after in vitro expansion of neural stem/progenitor cells and it is not present in vivo.
早期研究表明,来自一个体细胞组织的干细胞在通过移植交换其位置后,可能会产生另一个在胚胎学上不相关的组织的分化成分。两份报告指出,在补充生长因子的培养基中进行体外扩增后,克隆起源的小鼠和人类神经干细胞在注射到亚致死剂量照射的小鼠体内时,可能会维持造血功能。在这里,我们研究了新鲜解离的胎儿神经细胞(fNC)是否具有体外扩增神经细胞所报道的造血潜能。为了将造血污染的风险降至最低,供体细胞取自小鼠胚胎第10.5天发育中的大脑,此时血管尚未长入大脑;将直接来自表达增强型绿色荧光蛋白的转基因小鼠胎儿大脑的10(6)个fNC注射到亚致死剂量照射(6 Gy)的C57B16小鼠的尾静脉或直接注射到骨髓中。移植后,通过流式细胞术分析、聚合酶链反应以及对外周血和骨髓进行克隆形成干细胞检测,在不同存活时间评估供体来源细胞的存在情况。虽然移植后2周起就检测到骨髓来源的细胞,但移植神经胚胎细胞的小鼠在移植后长达16个月均未表现出任何向造血细胞转分化的迹象。我们的数据表明,如果存在从神经细胞向造血表型转分化的能力,那么这种能力只有在神经干/祖细胞体外扩增后才会获得,而在体内并不存在。