Neumeister Bettina, Grabosch Antje, Basak Onur, Kemler Rolf, Taylor Verdon
Department of Molecular Embryology, Max-Planck Institute of Immunobiology, Freiburg, Germany.
Stem Cells. 2009 Mar;27(3):714-23. doi: 10.1634/stemcells.2008-0985.
Somatic stem cells are reservoirs to replace lost cells or damaged tissue. Cells with neural stem cell (NSC) characteristics can be isolated from the postnatal mammalian brain into adulthood and expanded as neurospheres. We addressed the ability of these in vitro expanded putative NSCs to retain progenitor characteristics in vivo, in analogy to hematopoietic stem cells. When transplanted in utero, both postnatal and adult neural progenitors colonize host brains and contribute neurons and glia. In stark contrast to what has been reported when transplanted in postnatal hosts, epidermal growth factor-expanded cells also remain self-replicating and multipotent in vivo over many months and can be serially transplanted into multiple hosts. Surprisingly, embryonically transplanted NSCs remain in the neurogenic regions in adult hosts, where they express progenitor cell markers and continue to proliferate even after 6 months without tumor formation. These data indicate that spherogenic cells of the postnatal and adult mammalian brain retain their potential in vitro and in vivo throughout the life of the organism and beyond transplantation, which has important implications for cell replacement strategies.
体细胞干细胞是替代丢失细胞或受损组织的储备库。具有神经干细胞(NSC)特征的细胞可从出生后的哺乳动物大脑中分离出来,直至成年,并作为神经球进行扩增。我们探讨了这些体外扩增的假定神经干细胞在体内保持祖细胞特征的能力,这类似于造血干细胞。当在子宫内移植时,出生后的和成年的神经祖细胞都会定殖于宿主大脑,并产生神经元和神经胶质细胞。与在出生后宿主中移植时的报道形成鲜明对比的是,表皮生长因子扩增的细胞在体内多个月内也能保持自我复制和多能性,并且可以连续移植到多个宿主中。令人惊讶的是,胚胎期移植的神经干细胞在成年宿主的神经发生区域中留存,它们表达祖细胞标志物,甚至在6个月后仍继续增殖,且未形成肿瘤。这些数据表明,出生后的和成年的哺乳动物大脑中的成球细胞在生物体的整个生命过程中以及移植后,在体外和体内都保留了它们的潜能,这对细胞替代策略具有重要意义。