Safford Kristine M, Hicok Kevin C, Safford Shawn D, Halvorsen Yuan-Di C, Wilkison William O, Gimble Jeffrey M, Rice Henry E
Department of Surgery, Division of Pediatric Surgery, Box 3815, Duke University Medical Center, Durham, NC 27710, USA.
Biochem Biophys Res Commun. 2002 Jun 7;294(2):371-9. doi: 10.1016/S0006-291X(02)00469-2.
The identification of cells capable of neuronal differentiation has great potential for cellular therapies. We examined whether murine and human adipose-derived adult stem (ADAS) cells can be induced to undergo neuronal differentiation. We isolated ADAS cells from the adipose tissue of adult BalbC mice or from human liposuction tissue and induced neuronal differentiation with valproic acid, butylated hydroxyanisole, insulin, and hydrocortisone. As early as 1-3 h after neuronal induction, the phenotype of ADAS cells changed towards neuronal morphology. Following neuronal induction, muADAS cells displayed immunocytochemical staining for GFAP, nestin and NeuN and huADAS cells displayed staining for intermediate filament M, nestin, and NeuN. Following neuronal induction of murine and human ADAS cells, Western blot analysis confirmed GFAP, nestin, and NeuN protein expression. Pretreatment with EGF and basic FGF augmented the neuronal differentiation of huADAS cells. The neuronal differentiation of stromal cells from adipose tissue has broad biological and clinical implications.
鉴定能够进行神经元分化的细胞在细胞治疗方面具有巨大潜力。我们研究了小鼠和人类脂肪来源的成体干细胞(ADAS细胞)是否可被诱导进行神经元分化。我们从成年BalbC小鼠的脂肪组织或人类抽脂组织中分离出ADAS细胞,并用丙戊酸、丁基羟基茴香醚、胰岛素和氢化可的松诱导神经元分化。早在神经元诱导后1 - 3小时,ADAS细胞的表型就朝着神经元形态发生变化。神经元诱导后,小鼠ADAS细胞显示出针对GFAP、巢蛋白和NeuN的免疫细胞化学染色,而人类ADAS细胞显示出针对中间丝M、巢蛋白和NeuN的染色。对小鼠和人类ADAS细胞进行神经元诱导后,蛋白质印迹分析证实了GFAP、巢蛋白和NeuN蛋白的表达。用表皮生长因子(EGF)和碱性成纤维细胞生长因子(bFGF)预处理可增强人类ADAS细胞的神经元分化。脂肪组织来源的基质细胞的神经元分化具有广泛的生物学和临床意义。