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Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors
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 molecu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091697/ https://www.ncbi.nlm.nih.gov/pubmed/33941255 http://dx.doi.org/10.1186/s13287-021-02350-5 |
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author | Yi, Baicheng Ding, Tian Jiang, Shan Gong, Ting Chopra, Hitesh Sha, Ou Dissanayaka, Waruna Lakmal Ge, Shaohua Zhang, Chengfei |
author_facet | Yi, Baicheng Ding, Tian Jiang, Shan Gong, Ting Chopra, Hitesh Sha, Ou Dissanayaka, Waruna Lakmal Ge, Shaohua Zhang, Chengfei |
author_sort | Yi, Baicheng |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02350-5. |
format | Online Article Text |
id | pubmed-8091697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-80916972021-05-04 Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors Yi, Baicheng Ding, Tian Jiang, Shan Gong, Ting Chopra, Hitesh Sha, Ou Dissanayaka, Waruna Lakmal Ge, Shaohua Zhang, Chengfei Stem Cell Res Ther Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02350-5. BioMed Central 2021-05-03 /pmc/articles/PMC8091697/ /pubmed/33941255 http://dx.doi.org/10.1186/s13287-021-02350-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Yi, Baicheng Ding, Tian Jiang, Shan Gong, Ting Chopra, Hitesh Sha, Ou Dissanayaka, Waruna Lakmal Ge, Shaohua Zhang, Chengfei Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors |
title | Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors |
title_full | Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors |
title_fullStr | Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors |
title_full_unstemmed | Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors |
title_short | Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors |
title_sort | conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091697/ https://www.ncbi.nlm.nih.gov/pubmed/33941255 http://dx.doi.org/10.1186/s13287-021-02350-5 |
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