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

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.

An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration

“…Besides, the expression levels of IL-1β and TNF-α decreased within time in each group. On the other hand, IL-10 is a pro-healing cytokine, which can inhibit the function of T helper 1 (Th1) cell and reduce the production of pro-inflammatory cytokines [ 48 ]. The expression of IL-10 gradually increased over time, and iTE-scaffold group expressed higher IL-10 than NC and P-scaffold groups (Additional file 1 : Fig.…”

“…PDLSCs were cultured with EGM-2 (Lonza, Walkersville, USA) on different membranes for 7 days. In vitro angiogenic capacity was assessed by the tube formation assay on Matrigel (354230, Corning, NY, USA) as before [ 48 ]. PDLSCs in EGM-2, PDLSCs on P-scaffold, PDLSCs on iTE-scaffold and HUVECs were collected and resuspended in the medium of EGM-2.…”

Advanced materials and technologies for oral diseases

“…Since the nerve blood vessels in the pulp cavity provide nutrition for the hard tissue of the tooth and guide the development of the tooth root, more and more people are beginning to realize the importance of preserving the living pulp [ 85 ]. Therefore, new technologies have emerged as time requires, such as pulp revascularization, apical induction, pulp regeneration, and so on [ 68 , 86 ]. The basis for achieving these new technologies is the development of material science.…”

Endogenous Stem Cell‐Based In Situ Tissue Regeneration Using Electrostatically Interactive Hydrogel with a Newly Discovered Substance P Analog and VEGF‐Mimicking Peptide

“…Several groups have recently reported that MSCs such as adipose-derived MSCs, apical papilla mesenchymal stem cells, and dental pulp stem cells induced CD31-positive and vWF positive vasculogenic differentiation via VEGF, in addition to small molecules (e.g., VPA, forskolin). [42][43][44] Furthermore, several groups have reported that recruited MSCs or MSCs embedded in hydrogels can induce neo-vascularization in wound sites. [45][46][47] Compared to the complex structure of VEGF, VP has a short peptide sequence and therefore it is easy to produce, relatively inexpensive, and can be easily handled.…”