Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy
Diabetic retinopathy (DR) is characterized by morphologic and metabolic alterations in endothelial cells (ECs) and pericytes (PCs) of the blood–retinal barrier (BRB). The loss of interendothelial junctions, increased vascular permeability, microaneurysms, and finally, EC detachment are the main feat...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/913 |
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| author | Gabriella Lupo Aleksandra Agafonova Alessia Cosentino Giovanni Giurdanella Giuliana Mannino Debora Lo Furno Ivana Roberta Romano Rosario Giuffrida Floriana D’Angeli Carmelina Daniela Anfuso |
| author_facet | Gabriella Lupo Aleksandra Agafonova Alessia Cosentino Giovanni Giurdanella Giuliana Mannino Debora Lo Furno Ivana Roberta Romano Rosario Giuffrida Floriana D’Angeli Carmelina Daniela Anfuso |
| author_sort | Gabriella Lupo |
| collection | DOAJ |
| description | Diabetic retinopathy (DR) is characterized by morphologic and metabolic alterations in endothelial cells (ECs) and pericytes (PCs) of the blood–retinal barrier (BRB). The loss of interendothelial junctions, increased vascular permeability, microaneurysms, and finally, EC detachment are the main features of DR. In this scenario, a pivotal role is played by the extensive loss of PCs. Based on previous results, the aim of this study was to assess possible beneficial effects exerted by adipose mesenchymal stem cells (ASCs) and their pericyte-like differentiated phenotype (P-ASCs) on human retinal endothelial cells (HRECs) in high glucose conditions (25 mM glucose, HG). P-ASCs were more able to preserve BRB integrity than ASCs in terms of (a) increased transendothelial electrical resistance (TEER); (b) increased expression of adherens junction and tight junction proteins (VE-cadherin and ZO-1); (c) reduction in mRNA levels of inflammatory cytokines TNF-α, IL-1β, and MMP-9; (d) reduction in the angiogenic factor VEGF and in fibrotic TGF-β1. Moreover, P-ASCs counteracted the HG-induced activation of the pro-inflammatory phospho-ERK1/2/phospho-cPLA2/COX-2 pathway. Finally, crosstalk between HRECs and ASCs or P-ASCs based on the PDGF-B/PDGFR-β axis at the mRNA level is described herein. Thus, P-ASCs might be considered valuable candidates for therapeutic approaches aimed at countering BRB disruption in DR. |
| first_indexed | 2024-03-09T12:28:03Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:28:03Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bae509e528da4295b2329016713d7a1b2023-11-30T22:32:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124291310.3390/ijms24020913Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell TherapyGabriella Lupo0Aleksandra Agafonova1Alessia Cosentino2Giovanni Giurdanella3Giuliana Mannino4Debora Lo Furno5Ivana Roberta Romano6Rosario Giuffrida7Floriana D’Angeli8Carmelina Daniela Anfuso9Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, School of Medicine, University of Catania, 95123 Catania, ItalyFaculty of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Physiology, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Physiology, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Physiology, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Physiology, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, School of Medicine, University of Catania, 95123 Catania, ItalyDiabetic retinopathy (DR) is characterized by morphologic and metabolic alterations in endothelial cells (ECs) and pericytes (PCs) of the blood–retinal barrier (BRB). The loss of interendothelial junctions, increased vascular permeability, microaneurysms, and finally, EC detachment are the main features of DR. In this scenario, a pivotal role is played by the extensive loss of PCs. Based on previous results, the aim of this study was to assess possible beneficial effects exerted by adipose mesenchymal stem cells (ASCs) and their pericyte-like differentiated phenotype (P-ASCs) on human retinal endothelial cells (HRECs) in high glucose conditions (25 mM glucose, HG). P-ASCs were more able to preserve BRB integrity than ASCs in terms of (a) increased transendothelial electrical resistance (TEER); (b) increased expression of adherens junction and tight junction proteins (VE-cadherin and ZO-1); (c) reduction in mRNA levels of inflammatory cytokines TNF-α, IL-1β, and MMP-9; (d) reduction in the angiogenic factor VEGF and in fibrotic TGF-β1. Moreover, P-ASCs counteracted the HG-induced activation of the pro-inflammatory phospho-ERK1/2/phospho-cPLA2/COX-2 pathway. Finally, crosstalk between HRECs and ASCs or P-ASCs based on the PDGF-B/PDGFR-β axis at the mRNA level is described herein. Thus, P-ASCs might be considered valuable candidates for therapeutic approaches aimed at countering BRB disruption in DR.https://www.mdpi.com/1422-0067/24/2/913adipose mesenchymal stem cellspericyte-like differentiationretinal endothelial cellsblood–retinal barrierdiabetic retinopathyhyperglycemia |
| spellingShingle | Gabriella Lupo Aleksandra Agafonova Alessia Cosentino Giovanni Giurdanella Giuliana Mannino Debora Lo Furno Ivana Roberta Romano Rosario Giuffrida Floriana D’Angeli Carmelina Daniela Anfuso Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy International Journal of Molecular Sciences adipose mesenchymal stem cells pericyte-like differentiation retinal endothelial cells blood–retinal barrier diabetic retinopathy hyperglycemia |
| title | Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy |
| title_full | Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy |
| title_fullStr | Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy |
| title_full_unstemmed | Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy |
| title_short | Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy |
| title_sort | protective effects of human pericyte like adipose derived mesenchymal stem cells on human retinal endothelial cells in an in vitro model of diabetic retinopathy evidence for autologous cell therapy |
| topic | adipose mesenchymal stem cells pericyte-like differentiation retinal endothelial cells blood–retinal barrier diabetic retinopathy hyperglycemia |
| url | https://www.mdpi.com/1422-0067/24/2/913 |
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