Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors.
Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors.
复制标题
通过小分子和生长因子将根尖乳头干细胞转化为内皮细胞
DOI：
10.1186/s13287-021-02350-5
复制
发表时间：
2021-05-03
影响因子：
7.5
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Yi B;Ding T;Jiang S;Gong T;Chopra H;Sha O;Dissanayaka WL;Ge S;Zhang C
最近，一种新的策略被开发出来，使用小分子化合物直接将一种细胞类型重编程为另一种靶向细胞类型。人类成纤维细胞通过不同的小分子组合被化学重新编程为神经细胞、雪旺细胞和心肌细胞样细胞。本研究旨在探讨是否可以使用相同的策略将来自顶端乳头（SCAP）的干细胞重新编程为内皮细胞（ECs）。材料与方法采用RT-PCR、western blotting、流式细胞术和免疫荧光法检测化学诱导SCAP后内皮特异性基因和蛋白的表达水平。通过管状结构形成试验、乙酰化低密度脂蛋白（ac-LDL）摄取和NO分泌检测，评价scap来源的化学诱导内皮细胞（SCAP-ECs）体外功能。CCK-8和Transwell法检测SCAP-ECs的增殖和迁移能力。LPS刺激被用来模拟炎症环境，以证明scap - ec表达粘附分子的能力。利用免疫缺陷小鼠模型，采用体内Matrigel塞血管生成实验来评估SCAP-ECs在生成血管结构中的功能。结果scap - ecs表达上调的内皮特异性基因和蛋白；显示内皮转录网络；在体外表现出形成功能性管状结构、摄取ac-LDL和分泌NO的能力；并促进了体内血管的生成。SCAP-ECs还可以在促炎环境中表达粘附分子，并具有与HUVECs相似的迁移和增殖能力。结论研究表明，小分子和生长因子能显著促进SCAP内皮转分化，为血管工程和缺血性疾病的治疗提供了一个有希望的候选细胞来源。
ObjectivesRecently, a new strategy has been developed to directly reprogram one cell type towards another targeted cell type using small molecule compounds. Human fibroblasts have been chemically reprogrammed into neuronal cells, Schwann cells and cardiomyocyte-like cells by different small molecule combinations. This study aimed to explore whether stem cells from apical papilla (SCAP) could be reprogrammed into endothelial cells (ECs) using the same strategy.Materials and methodsThe expression level of endothelial-specific genes and proteins after chemical induction of SCAP was assessed by RT-PCR, western blotting, flow cytometry and immunofluorescence. The in vitro functions of SCAP-derived chemical-induced endothelial cells (SCAP-ECs) were evaluated by tube-like structure formation assay, acetylated low-density lipoprotein (ac-LDL) uptake and NO secretion detection. The proliferation and the migration ability of SCAP-ECs were evaluated by CCK-8 and Transwell assay. LPS stimulation was used to mimic the inflammatory environment in demonstrating the ability of SCAP-ECs to express adhesion molecules. The in vivo Matrigel plug angiogenesis assay was performed to assess the function of SCAP-ECs in generating vascular structures using the immune-deficient mouse model.ResultsSCAP-ECs expressed upregulated endothelial-specific genes and proteins; displayed endothelial transcriptional networks; exhibited the ability to form functional tubular-like structures, uptake ac-LDL and secrete NO in vitro; and contributed to generate blood vessels in vivo. The SCAP-ECs could also express adhesion molecules in the pro-inflammatory environment and have a similar migration and proliferation ability as HUVECs.ConclusionsOur study demonstrates that the set of small molecules and growth factors could significantly promote endothelial transdifferentiation of SCAP, which provides a promising candidate cell source for vascular engineering and treatment of ischemic diseases.
登录
查看更多内容
影响因子：
4
作者：
Rodas-Junco BA;Canul-Chan M;Rojas-Herrera RA;De-la-Peña C;Nic-Can GI
通讯作者：
Nic-Can GI
影响因子：
37.8
作者：
Han, Jung-Kyu;Chang, Sung-Hwan;Kim, Hyo-Soo
通讯作者：
Kim, Hyo-Soo
影响因子：
5.9
作者：
Thoma, Eva C.;Merkl, Claudia;Heckel, Tobias;Haab, Rachel;Knoflach, Frederic;Nowaczyk, Corinne;Flint, Nicholas;Jagasia, Ravi;Zoffmann, Sannah Jensen;Truong, Hoa Hue;Petitjean, Pascal;Jessberger, Sebastian;Graf, Martin;Iacone, Roberto
通讯作者：
Iacone, Roberto
影响因子：
56.9
作者：
Cao, Nan;Huang, Yu;Ding, Sheng
通讯作者：
Ding, Sheng
影响因子：
5.2
作者：
Goldman, Orit;Feraud, Olivier;Uzan, Georges
通讯作者：
Uzan, Georges