Gage F H, Coates P W, Palmer T D, Kuhn H G, Fisher L J, Suhonen J O, Peterson D A, Suhr S T, Ray J
Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11879-83. doi: 10.1073/pnas.92.25.11879.
The dentate gyrus of the hippocampus is one of the few areas of the adult brain that undergoes neurogenesis. In the present study, cells capable of proliferation and neurogenesis were isolated and cultured from the adult rat hippocampus. In defined medium containing basic fibroblast growth factor (FGF-2), cells can survive, proliferate, and express neuronal and glial markers. Cells have been maintained in culture for 1 year through multiple passages. These cultured adult cells were labeled in vitro with bromodeoxyuridine and adenovirus expressing beta-galactosidase and were transplanted to the adult rat hippocampus. Surviving cells were evident through 3 months postimplantation with no evidence of tumor formation. Within 2 months postgrafting, labeled cells were found in the dentate gyrus, where they differentiated into neurons only in the intact region of the granule cell layer. Our results indicate that FGF-2 responsive progenitors can be isolated from the adult hippocampus and that these cells retain the capacity to generate mature neurons when grafted into the adult rat brain.
海马体的齿状回是成年大脑中少数经历神经发生的区域之一。在本研究中,从成年大鼠海马体中分离并培养出了能够增殖和进行神经发生的细胞。在含有碱性成纤维细胞生长因子(FGF - 2)的特定培养基中,细胞能够存活、增殖并表达神经元和神经胶质细胞标志物。这些细胞已经通过多次传代在培养中维持了1年。这些培养的成年细胞在体外用溴脱氧尿苷和表达β - 半乳糖苷酶的腺病毒进行标记,然后移植到成年大鼠海马体中。移植后3个月内可见存活细胞,且没有肿瘤形成的迹象。移植后2个月内,在齿状回中发现了标记细胞,它们仅在颗粒细胞层的完整区域分化为神经元。我们的结果表明,FGF - 2反应性祖细胞可以从成年海马体中分离出来,并且这些细胞在移植到成年大鼠大脑中时保留了产生成熟神经元的能力。