Neurosurgery Institute of Guangdong, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Neurochem Res. 2010 Apr;35(4):572-9. doi: 10.1007/s11064-009-0101-y. Epub 2009 Dec 4.
The aim of this study was to compare the neural differentiation potential and the expression of neurotrophic factors (NTFs) in differentiated adipose-derived stem cells (ADSCs) using three established induction protocols, serum free (Protocol 1), chemical reagents (Protocol 2), and spontaneous (Protocol 3) protocols. Protocol 1 produced the highest percentage of mature neural-like cells (MAP2ab(+)). Protocol 2 showed the highest percentage of immature neural-like cells (beta-tubulin III(+)), but the neural-like state was transient and reversible. Protocol 3 caused ADSCs to differentiate spontaneously into immature neural-like cells, but not into mature neural cell types. The neural-like cells produced by Protocol 1 lived the longest in culture with little cell death, but Protocol 2 and 3 led to the significant cell death. Therefore, Protocol 1 is the most efficient among these protocols. Additionally, soon after differentiation, the mRNA levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in dADSCs were sharply decreased by Protocol 1 and 2 (acute induction protocol), but not by Protocol 3 (chronic induction protocol). The results indicate that NTFs played an important role in neural differentiation via acute responses to NGF and BDNF, but not chronically during the transdifferentiation process.
本研究旨在比较三种已建立的诱导方案(无血清方案 1、化学试剂方案 2 和自发方案 3)中脂肪来源干细胞(ADSCs)的神经分化潜能和神经营养因子(NTFs)的表达。方案 1 产生了最高比例的成熟神经样细胞(MAP2ab(+))。方案 2 显示了最高比例的不成熟神经样细胞(β-微管蛋白 III(+)),但神经样状态是短暂和可逆的。方案 3 导致 ADSCs 自发分化为不成熟的神经样细胞,但不能分化为成熟的神经细胞类型。方案 1 诱导产生的神经样细胞在培养中存活时间最长,细胞死亡较少,但方案 2 和 3 导致明显的细胞死亡。因此,方案 1 是这些方案中最有效的。此外,在分化后不久,方案 1 和 2(急性诱导方案)迅速降低了诱导分化的 dADSCs 中神经生长因子(NGF)和脑源性神经营养因子(BDNF)的 mRNA 水平,但方案 3(慢性诱导方案)没有。这些结果表明,NTFs 通过对 NGF 和 BDNF 的急性反应在神经分化中发挥重要作用,但在转分化过程中并不持续。