Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors

Stem Cell Research & Therapy

Ting Gong¹  Shan Jiang²  Chengfei Zhang³  Tian Ding⁴  Waruna Lakmal Dissanayaka⁵  Baicheng Yi⁵  Hitesh Chopra⁵  Ou Sha⁵  Shaohua Ge⁶ 

[1] Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration;Shandong Key Laboratory of Oral Tissue Regeneration;Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, The University of Hong Kong;Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University;Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong;School of Dentistry, Shenzhen University Health Science Center;

关键词: SCAP;    Endothelial differentiation;    Small molecules;    Chemical reprogramming;    Angiogenesis;   

DOI  :  10.1186/s13287-021-02350-5

来源: DOAJ

【 摘 要 】

Abstract Objectives Recently, 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 methods The 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. Results SCAP-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. Conclusions Our 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.

【 授权许可】

Unknown