Growth Factors and Small-molecule Compounds in Derivation of Endothelial Lineages from Dental Stem Cells.
Growth Factors and Small-molecule Compounds in Derivation of Endothelial Lineages from Dental Stem Cells.
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DOI：
10.1016/j.joen.2020.06.024
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发表时间：
2020-09
影响因子：
4.2
通讯作者：
B. Yi;Waruna Lakmal Dissanayaka;Chengfei Zhang
中科院分区：
文献类型：
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作者：
B. Yi;Waruna Lakmal Dissanayaka;Chengfei Zhang
将完全组装的微血管网络整合到生物工程牙髓结构中可以显著提高移植后的功能性血流量和组织存活率。内皮细胞（ECs）是血管组织的细胞构件，在血管预形成过程中起着至关重要的作用。然而，从合适的来源获得足够的ECs用于翻译应用是具有挑战性的。牙干细胞（DSCs）由于其自身来源而表现出强大的增殖能力和免疫相容性，可能是内皮细胞谱系衍生的一个有前途的替代细胞来源。在特定的培养条件下，dsc分化为成骨/牙源性、脂肪源性、软骨源性和神经源性细胞系。方法近年来发展了一种利用化学混合物和生长因子直接重编程细胞的新方法。与传统的基于外源转录因子强制表达的重编程方法相比，化学策略避免了与慢病毒转导相关的风险，同时提供了一种更可行的方法来驱动细胞谱系转换。这篇综述的目的是揭示利用小分子化合物和生长因子调节关键信号通路从dsc中获得ec的概念。结果本研究初步发现，小分子化合物和生长因子可诱导根尖乳头干细胞分化为上皮样细胞。这些ec样细胞在体外表达内皮特异性基因（CD31和vegfr2）和蛋白（CD31、VEGF受体2和血管内皮钙粘蛋白），并产生血管样管状结构。结论化学重编程可能为牙干细胞生成ec样细胞提供了一种新的途径。
IntroductionIncorporating fully assembled microvascular networks into bioengineered dental pulp constructs can significantly enhance functional blood flow and tissue survival upon transplantation. Endothelial cells (ECs), cellular building blocks of vascular tissue, play an essential role in the process of prevascularization. However, obtaining sufficient ECs from a suitable source for translational application is challenging. Dental stem cells (DSCs), which exhibit a robust proliferative ability and immunocompatibility because of their autologous origin, could be a promising alternative cell source for the derivation of endothelial lineages. Under specific culture conditions, DSCs differentiate into osteo/odontogenic, adipogenic, chondrogenic, and neurogenic cell lineages.MethodsRecently, a new approach has been developed to directly reprogram cells using chemical cocktails and growth factors. Compared with the traditional reprogramming approach based on the forced expression of exogenous transcription factors, the chemical strategy avoids the risk associated with lentiviral transduction while offering a more viable methodology to drive cell lineage switch. The aim of this review was to unveil the concept of the use of small-molecule compounds and growth factors modulating key signaling pathways to derive ECs from DSCs.ResultsIn addition, our preliminary study showed that stem cells from the apical papilla could be induced into EC-like cells using small-molecule compounds and growth factors. These EC-like cells expressed endothelial specific genes (CD31andVEGFR2) and proteins (CD31, VEGF receptor 2, and vascular endothelial cadherin) as well as gave rise to vessel-like tubular structuresin vitro.ConclusionsOur preliminary results suggest that chemical reprogramming might offer a novel way to generate EC-like cells from dental stem cells.