Ectopic transient overexpression of facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells

Limitation in cell sources for autologous cell therapy has been a recent focus in stem cell therapy and tissue engineering. Among various research advances, direct conversion, or transdifferentiation, is a notable and feasible strategy for the generation and acquirement of wanted cell source. So far...

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Main Authors: Seung Hyun L Kim, Seunghun S Lee, Inseon Kim, Janet Kwon, Song Kwon, Taegeun Bae, Junho Hur, Hwajin Lee, Nathaniel S Hwang
Format: Article
Language:English
Published: SAGE Publishing 2020-03-01
Series:Journal of Tissue Engineering
Online Access:https://doi.org/10.1177/2041731420909208
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author Seung Hyun L Kim
Seunghun S Lee
Inseon Kim
Janet Kwon
Song Kwon
Taegeun Bae
Junho Hur
Hwajin Lee
Nathaniel S Hwang
author_facet Seung Hyun L Kim
Seunghun S Lee
Inseon Kim
Janet Kwon
Song Kwon
Taegeun Bae
Junho Hur
Hwajin Lee
Nathaniel S Hwang
author_sort Seung Hyun L Kim
collection DOAJ
description Limitation in cell sources for autologous cell therapy has been a recent focus in stem cell therapy and tissue engineering. Among various research advances, direct conversion, or transdifferentiation, is a notable and feasible strategy for the generation and acquirement of wanted cell source. So far, utilizing cell transdifferentiation technology in tissue engineering was mainly restricted at achieving single wanted cell type from diverse cell types with high efficiency. However, regeneration of a complete tissue always requires multiple cell types which poses an intrinsic complexity. In this study, enhanced osteogenic differentiation was achieved by transient ectopic expression of octamer-binding transcription factor 4 ( OCT-4 ) gene followed by bone morphogenetic protein 4 treatment on human umbilical vein endothelial cells. OCT-4 transfection and bone morphogenetic protein 4 treatment resulted in enhanced expression of osteogenic markers such as core-binding factor alpha 1, alkaline phosphatase, and collagen 1 compared with bone morphogenetic protein 4 treatment alone. Furthermore, we employed gelatin-heparin cryogel in cranial defect model for in vivo bone formation. Micro-computed tomography and histological analysis of in vivo samples showed that OCT-4 transfection followed by bone morphogenetic protein 4 treatment resulted in efficient transdifferentiation of endothelial cells to osteogenic cells. These results suggest that the combination of OCT-4 and bone morphogenetic protein 4 on endothelial cells would be a reliable multicellular transdifferentiation model which could be applied for bone tissue engineering.
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spelling doaj.art-3db085025e654e2dada2b17bcd641af42022-12-21T18:59:22ZengSAGE PublishingJournal of Tissue Engineering2041-73142020-03-011110.1177/2041731420909208Ectopic transient overexpression of facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cellsSeung Hyun L Kim0Seunghun S Lee1Inseon Kim2Janet Kwon3Song Kwon4Taegeun Bae5Junho Hur6Hwajin Lee7Nathaniel S Hwang8Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of KoreaInterdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of KoreaSchool of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, Republic of KoreaInterdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of KoreaSchool of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, Republic of KoreaBioMAX/N-Bio Institute, Seoul National University, Seoul, Republic of KoreaDepartment of Medicine, Kyung Hee University, Seoul, Republic of KoreaSchool of Dentistry, Seoul National University, Seoul, Republic of KoreaBioMAX/N-Bio Institute, Seoul National University, Seoul, Republic of KoreaLimitation in cell sources for autologous cell therapy has been a recent focus in stem cell therapy and tissue engineering. Among various research advances, direct conversion, or transdifferentiation, is a notable and feasible strategy for the generation and acquirement of wanted cell source. So far, utilizing cell transdifferentiation technology in tissue engineering was mainly restricted at achieving single wanted cell type from diverse cell types with high efficiency. However, regeneration of a complete tissue always requires multiple cell types which poses an intrinsic complexity. In this study, enhanced osteogenic differentiation was achieved by transient ectopic expression of octamer-binding transcription factor 4 ( OCT-4 ) gene followed by bone morphogenetic protein 4 treatment on human umbilical vein endothelial cells. OCT-4 transfection and bone morphogenetic protein 4 treatment resulted in enhanced expression of osteogenic markers such as core-binding factor alpha 1, alkaline phosphatase, and collagen 1 compared with bone morphogenetic protein 4 treatment alone. Furthermore, we employed gelatin-heparin cryogel in cranial defect model for in vivo bone formation. Micro-computed tomography and histological analysis of in vivo samples showed that OCT-4 transfection followed by bone morphogenetic protein 4 treatment resulted in efficient transdifferentiation of endothelial cells to osteogenic cells. These results suggest that the combination of OCT-4 and bone morphogenetic protein 4 on endothelial cells would be a reliable multicellular transdifferentiation model which could be applied for bone tissue engineering.https://doi.org/10.1177/2041731420909208
spellingShingle Seung Hyun L Kim
Seunghun S Lee
Inseon Kim
Janet Kwon
Song Kwon
Taegeun Bae
Junho Hur
Hwajin Lee
Nathaniel S Hwang
Ectopic transient overexpression of facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
Journal of Tissue Engineering
title Ectopic transient overexpression of facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
title_full Ectopic transient overexpression of facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
title_fullStr Ectopic transient overexpression of facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
title_full_unstemmed Ectopic transient overexpression of facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
title_short Ectopic transient overexpression of facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
title_sort ectopic transient overexpression of facilitates bmp4 induced osteogenic transdifferentiation of human umbilical vein endothelial cells
url https://doi.org/10.1177/2041731420909208
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