根尖牙乳头干细胞 (Stem cells from apical papilla, SCAP) 具有多向分化潜能，极有可能作为成骨、成血管和成神经等的种子细胞。研究如何促进SCAP向血管内皮细胞高效、稳定分化，获得大量的可临床应用的内皮细胞，能为牙髓血管再生等组织工程和其他缺血性疾病的治疗提供关键的细胞来源。小分子化合物介导的转分化（化学重编程）是一种有广阔前景的、可以改变体细胞谱系命运的方法。已有研究表明，使用小分子化合物组合及特定培养条件，体细胞可被诱导成为各种谱系的目的细胞，如神经前体细胞，神经元细胞、心肌细胞等。我们的研究亦表明，牙源性干细胞具有一定的内皮细胞向分化潜能，但其诱导分化效率较低。本课题拟在前期研究的基础上，优化小分子化合物组合，结合血管内皮生长因子和内皮细胞的特异培养环境，以期高效获得SCAP来源的血管内皮细胞，并进一步研究其细胞特性、体内外功能以及该过程的分子机制。

Stem cells from apical papilla (SCAP) are potentially promising cell sources for tissue engineering due to the isolation with minimal invasiveness and immunocompatibility with autologous origin. SCAP exhibits high proliferation and multipotency. SCAP could differentiate into odontogenic/osteogenic, endothelial and neural-like cells. Endothelial cells (ECs) are the principal building blocks forming the inner layer of blood vessels. However, to generate sufficient numbers of transplantable ECs for translational applications is extremely challenging. Our previous studies demonstrated that dental stem cells showed some extent of potential to differentiate into ECs, but the efficiency of the induction need to be improved. Recently, a new approach has been developed for direct reprogramming one cell type into another targeted cell type with chemical cocktail (chemical reprogramming). Compared with the transgenic approach to induce lineage reprogramming, the chemical reprogramming approach provides a more promising methodology for driving cell lineage switch, avoiding the risk of lentivirus involvement and genome integration through the use of exogenous transcriptional factors. Small molecule compounds are cell permeable, easily synthesized and preserved, and can be precisely controlled in terms of concentration, duration, and combination. Human fibroblasts have been chemically reprogrammed into neural progenitor cells, neuron cells and cardiomyocyte-like cells by different small molecule combinations. It is rational to hypothesize that dental stem cells could be chemical reprogrammed into ECs. The objectives of the present proposal are to induce SCAP to ECs with a set of chemical cocktail we developed, and provide a safe and functional approach to get the candidate cell source for therapeutic angiogenesis.