Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
Neurosci Lett. 2013 Feb 28;539:86-91. doi: 10.1016/j.neulet.2013.01.046. Epub 2013 Feb 8.
We have reported that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are capable of differentiating into dopaminergic (DA) neuron-like cells upon being induced by amniotic epithelial cells (AECs). However, what factor(s) is involved in the differentiation process has not been explored out thoroughly. Because pleiotrophin (PTN) is known to exert important trophic effects on DA neurons, in the present study, we investigated whether PTN is released by AECs and whether it is involved in the differentiation of hUCB-MSCs into DA neuron-like cells. The expression and secretion of PTN by AECs were detected by immunofluorescence, RT-PCR and ELISA. The hUCB-MSCs were isolated and treated with AEC-conditioned medium (ACM) or recombinant human PTN. Compared to the controls, a higher proportion of treated cells differentiated into DA neuron-like cells, indicated by the increased expression of TH and DAT and the increased dopamine content. These results indicate that PTN released by AECs acts as a synergetic factor with other neurotrophic factors and is involved in the differentiation of hUCB-MSCs into DA neuron-like cells. We suggest that ACM, which contains PTN and other neurotrophic factors, could potentially be used as an agent to promote the differentiation of DA neuron-like cells from hUCB-MSCs for cell therapy of Parkinson's disease without creating legal or ethical issues.
我们曾报道过,人脐带血间充质干细胞(hUCB-MSCs)在羊膜上皮细胞(AECs)的诱导下能够分化为多巴胺能(DA)神经元样细胞。然而,分化过程中涉及到哪些因素还没有被充分探索。由于多效蛋白(PTN)已知对 DA 神经元具有重要的营养作用,因此在本研究中,我们研究了 AEC 是否释放 PTN 以及它是否参与 hUCB-MSCs 向 DA 神经元样细胞的分化。通过免疫荧光、RT-PCR 和 ELISA 检测 AEC 中 PTN 的表达和分泌。分离 hUCB-MSCs 并与 AEC 条件培养基(ACM)或重组人 PTN 一起处理。与对照组相比,更多的处理细胞分化为 DA 神经元样细胞,这表现为 TH 和 DAT 的表达增加以及多巴胺含量增加。这些结果表明,AEC 释放的 PTN 作为一种协同因子与其他神经营养因子一起,参与 hUCB-MSCs 向 DA 神经元样细胞的分化。我们建议,包含 PTN 和其他神经营养因子的 ACM 可作为一种促进 hUCB-MSCs 向 DA 神经元样细胞分化的试剂,用于治疗帕金森病的细胞治疗,而不会产生法律或伦理问题。