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间充质干细胞的条件培养基可促进视网膜祖细胞的增殖、黏附和神经元分化。

The condition medium of mesenchymal stem cells promotes proliferation, adhesion and neuronal differentiation of retinal progenitor cells.

作者信息

Zhang Mingqi, Zhang Fenglei, Sun Jin, Sun Yan, Xu Ling, Zhang Donglei, Wang Zhuoshi, He Wei

机构信息

Clinical Research Center, HE Eye Hospital of HE University, Shenyang, Liaoning Province, People's Republic of China.

College of Basic Medicine, HE University, Shenyang, Liaoning Province, People's Republic of China.

出版信息

Neurosci Lett. 2017 Sep 14;657:62-68. doi: 10.1016/j.neulet.2017.07.053. Epub 2017 Jul 31.

DOI:10.1016/j.neulet.2017.07.053
PMID:28774569
Abstract

Retinal progenitor cell is a promising candidate in the treatment of retinal pigmentosa diseases. The limiting factors of stem cell transplantation are the proliferation and differentiation capacities of hRPCs, which may be governed by culture conditions. Previous studies have proved that the secretome of human Umbilical Cord Mesenchymal stem cells (hUCMSCs) and human Adipose derived stem cells (hADSCs), including more active cytokines and neurotrophic factors, have the paracrine potential of enhancing proliferation and differentiation in several cell types. The aim of this study was to investigate whether hRPCs could effectively proliferate, adhere and differentiate towards specific retinal cell types by treating with the condition medium (CM) of hUCMSCs (hUCMSCCM) or hADSCs (hADSCCM). Here, we show that hUCMSCCM or hADSCCM enhances the proliferation rate of the S and G2 phase cells, with an upregulation of Ki67 expression. Moreover, the upregulation expression of NF, Recoverin and Rhodopsin indicates that specialized retinal cells including ganglion cells and photoreceptors are favored over hRPCs differentiation due to hUCMSCCM or hADSCCM. Under FBS induced differentiation conditions, hRPCs treated with hUCMSCCM or hADSCCM increase the expression of retinal neuron and photoreceptor specific markers. These results suggest that hUCMSCCM and hADSCCM can stimulate the hRPC proliferation, promote its adherence and support hRPC neuronal and photoreceptor differentiation. These findings may provide a new strategy to improve the viability of hRPCs and photoreceptor differentiation capacities.

摘要

视网膜祖细胞是治疗视网膜色素变性疾病的一个有前景的候选者。干细胞移植的限制因素是人类视网膜祖细胞(hRPCs)的增殖和分化能力,而这可能受培养条件的调控。先前的研究已经证明,人脐带间充质干细胞(hUCMSCs)和人脂肪来源干细胞(hADSCs)的分泌组,包括更具活性的细胞因子和神经营养因子,具有增强几种细胞类型增殖和分化的旁分泌潜力。本研究的目的是调查通过用人脐带间充质干细胞条件培养基(hUCMSCCM)或人脂肪来源干细胞条件培养基(hADSCCM)处理,hRPCs是否能有效地增殖、黏附并向特定视网膜细胞类型分化。在此,我们表明hUCMSCCM或hADSCCM提高了S期和G2期细胞的增殖率,同时Ki67表达上调。此外,NF、恢复蛋白和视紫红质的表达上调表明,由于hUCMSCCM或hADSCCM,包括神经节细胞和光感受器在内的特化视网膜细胞更有利于hRPCs的分化。在胎牛血清诱导的分化条件下,用hUCMSCCM或hADSCCM处理的hRPCs增加了视网膜神经元和光感受器特异性标志物的表达。这些结果表明,hUCMSCCM和hADSCCM可以刺激hRPCs的增殖,促进其黏附,并支持hRPCs向神经元和光感受器分化。这些发现可能为提高hRPCs的活力和光感受器分化能力提供一种新策略。

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