Luzuriaga Jon, Pastor-Alonso Oier, Encinas Juan Manuel, Unda Fernando, Ibarretxe Gaskon, Pineda Jose Ramon
Signaling Lab, Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain.
Laboratory of Neural Stem Cells and Neurogenesis, Achucarro Basque Center for Neuroscience, Leioa, Spain.
Front Physiol. 2019 Mar 28;10:347. doi: 10.3389/fphys.2019.00347. eCollection 2019.
Dental pulp stem cells (DPSCs) have the capacity to give rise to cells with neuronal-like phenotypes, suggesting their use in brain cell therapies. In the present work, we wanted to address the phenotypic fate of adult genetically unmodified human DPSCs cultured in Neurocult (Stem Cell Technologies), a cell culture medium without serum which can be alternatively supplemented for the expansion and/or differentiation of adult neural stem cells (NSCs). Our results show that non-genetically modified human adult DPSCs cultured with Neurocult NS-A proliferation supplement generated neurosphere-like dentospheres expressing the NSC markers Nestin and glial fibrillary acidic protein (GFAP), but also the vascular endothelial cell marker CD31. Remarkably, 1 month after intracranial graft into athymic nude mice, human CD31+/CD146+ and Nestin+ DPSC-derived cells were found tightly associated with both the endothelial and pericyte layers of brain vasculature, forming full blood vessels of human origin which showed an increased laminin staining. These results are the first demonstration that DPSC-derived cells contributed to the generation of neovasculature within brain tissue, and that Neurocult and other related serum-free cell culture media may constitute a fast and efficient way to obtain endothelial cells from human DPSCs.
牙髓干细胞（DPSCs）具有分化为具有神经元样表型细胞的能力，这表明它们可用于脑细胞治疗。在本研究中，我们想探究在Neurocult（干细胞技术公司）中培养的成年未基因修饰的人类DPSCs的表型命运，Neurocult是一种无血清的细胞培养基，可用于成年神经干细胞（NSCs）的扩增和/或分化。我们的结果表明，用Neurocult NS - A增殖补充剂培养的未基因修饰的人类成年DPSCs产生了表达NSC标志物巢蛋白（Nestin）和胶质纤维酸性蛋白（GFAP）的神经球样牙本质球，但也表达血管内皮细胞标志物CD31。值得注意的是，将其颅内移植到无胸腺裸鼠体内1个月后，发现人类CD31 + / CD146 +和Nestin + DPSC衍生细胞与脑血管的内皮细胞层和周细胞层紧密相关，形成了具有人类来源的完整血管，其层粘连蛋白染色增加。这些结果首次证明DPSC衍生细胞有助于脑组织内新血管的生成，并且Neurocult和其他相关的无血清细胞培养基可能构成从人类DPSCs获得内皮细胞的快速有效方法。
