Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo

AIM: To investigate the effect of the overexpression of C-X-C chemokine receptor type 4 (CXCR4) on homing of mesenchymal stem cells (MSCs) in vitro and therapeutic effects of diabetic retinopathy (DR) in vivo. METHODS: MSCs were infected by lentivirus constructed with CXCR4. The expression of CXCR4...

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Main Authors: Jian Wang, Wei Zhang, Guang-Hui He, Bin Wu, Song Chen
Format: Article
Language:English
Published: Press of International Journal of Ophthalmology (IJO PRESS) 2018-05-01
Series:International Journal of Ophthalmology
Subjects:
Online Access:http://www.ijo.cn/en_publish/2018/5/20180508.pdf
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author Jian Wang
Wei Zhang
Guang-Hui He
Bin Wu
Song Chen
author_facet Jian Wang
Wei Zhang
Guang-Hui He
Bin Wu
Song Chen
author_sort Jian Wang
collection DOAJ
description AIM: To investigate the effect of the overexpression of C-X-C chemokine receptor type 4 (CXCR4) on homing of mesenchymal stem cells (MSCs) in vitro and therapeutic effects of diabetic retinopathy (DR) in vivo. METHODS: MSCs were infected by lentivirus constructed with CXCR4. The expression of CXCR4 was examined by immunofluorescence, Western blot, and quantitative polymerase chain reaction. CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis, migration, and apoptotic activities. CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR. The histological structure of DR in rats was inspected by hematoxylin and eosin staining. The expression of rhodopsin, neuron-specific enolase (NSE), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α was examined by Western blot and immunohistochemical analyses. RESULTS: The transduction of MSCs by lentivirus was effective, and the transduced MSCs had high expression levels of CXCR4 gene and protein. Improved migration activities were observed in CXCR4-overexpressing MSCs. Further, reduced retinal damage, upregulation of rhodopsin and NSE protein, and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo. CONCLUSION: The homing of MSCs can be enhanced by upregulating CXCR4 levels, possibly improving histological structures of DR. CXCR4-overexpressing MSCs can be a novel strategy for treating DR.
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spelling doaj.art-890387ea821e46d3abf46d6e7bbde35d2022-12-22T03:23:37ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982018-05-0111576677210.18240/ijo.2018.05.08Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivoJian Wang0Wei Zhang1Guang-Hui He2Bin Wu3Song Chen4Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin 300020, ChinaTianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin 300020, ChinaTianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin 300020, ChinaTianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin 300020, ChinaTianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin 300020, ChinaAIM: To investigate the effect of the overexpression of C-X-C chemokine receptor type 4 (CXCR4) on homing of mesenchymal stem cells (MSCs) in vitro and therapeutic effects of diabetic retinopathy (DR) in vivo. METHODS: MSCs were infected by lentivirus constructed with CXCR4. The expression of CXCR4 was examined by immunofluorescence, Western blot, and quantitative polymerase chain reaction. CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis, migration, and apoptotic activities. CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR. The histological structure of DR in rats was inspected by hematoxylin and eosin staining. The expression of rhodopsin, neuron-specific enolase (NSE), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α was examined by Western blot and immunohistochemical analyses. RESULTS: The transduction of MSCs by lentivirus was effective, and the transduced MSCs had high expression levels of CXCR4 gene and protein. Improved migration activities were observed in CXCR4-overexpressing MSCs. Further, reduced retinal damage, upregulation of rhodopsin and NSE protein, and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo. CONCLUSION: The homing of MSCs can be enhanced by upregulating CXCR4 levels, possibly improving histological structures of DR. CXCR4-overexpressing MSCs can be a novel strategy for treating DR.http://www.ijo.cn/en_publish/2018/5/20180508.pdf772chemokine receptor type 4diabetic retinopathymesenchymal stem cellstransplantation
spellingShingle Jian Wang
Wei Zhang
Guang-Hui He
Bin Wu
Song Chen
Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo
International Journal of Ophthalmology
772
chemokine receptor type 4
diabetic retinopathy
mesenchymal stem cells
transplantation
title Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo
title_full Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo
title_fullStr Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo
title_full_unstemmed Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo
title_short Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo
title_sort transfection with cxcr4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo
topic 772
chemokine receptor type 4
diabetic retinopathy
mesenchymal stem cells
transplantation
url http://www.ijo.cn/en_publish/2018/5/20180508.pdf
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