Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells
Introduction: Glaucoma is a vision-threatening disease associated with accelerated aging of trabecular meshwork (TM) which results in elevated intraocular pressure (IOP). Increased oxidative stress in TM plays an important role in cellular molecular damage which leads to senescence. Autophagy is an...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320422001249 |
| _version_ | 1811154721609613312 |
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| author | Yu-Fan Chang Yung-Hsin Cheng Yu-Chieh Ko Shih-Hwa Chiou Catherine Jui-Ling Liu |
| author_facet | Yu-Fan Chang Yung-Hsin Cheng Yu-Chieh Ko Shih-Hwa Chiou Catherine Jui-Ling Liu |
| author_sort | Yu-Fan Chang |
| collection | DOAJ |
| description | Introduction: Glaucoma is a vision-threatening disease associated with accelerated aging of trabecular meshwork (TM) which results in elevated intraocular pressure (IOP). Increased oxidative stress in TM plays an important role in cellular molecular damage which leads to senescence. Autophagy is an intracellular lysosomal degradation process which is activated when cells are under stressful condition, and emerging studies have demonstrated increased expression of modulators of apoptosis and expression of autophagic cascade in ex-vivo TM specimens or cultured TM cells under oxidative stress. Recently, studies have shown neuroprotective and IOP-lowering effects after transplanting mesenchymal stem cells (MSCs) or injecting condition medium (CM) of MSCs into ocular hypertension animal models. However, knowledge of the underlying mechanism accounting for these effects is limited. Using condition medium (CM) from human bone marrow-derived mesenchymal stem cells (BM-MSCs), we investigated the effects of the CM derived from BM-MSCs on TM autophagy and apoptosis. Methods: H2O2 was added to culture medium of human TM cells to mimic oxidative damage in glaucomatous eyes, and the autophagic and anti-apoptotic effects of BM-MSCs-derived CM was explored on the oxidatively damaged cells. Mitochondrial ROS production was examined by MitoSOX™, apoptosis was evaluated using terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) staining, and the expression of proteins involved in autophagy as well as extracellular matrix was investigated via Western blot. Results: There were no significant differences in TM cell viability when the cells were treated with different concentrations of CM in the absence of oxidative stress. Cell viability was significantly higher in oxidatively damaged TM cells treated with 1X or 5X CM compared to untreated TM cells under oxidative stress. The mitochondrial ROS level significantly increased with oxidative stress, which was mitigated in the CM treatment groups. DNA fragmentation significantly decreased in oxidatively stressed TM cells after treatment with CM. LCB3 II/LCB3 I was significantly elevated in the oxidative stress group compared to the control group and was significantly decreased in the CM treatment groups. Expression of fibronectin was not significantly different among the groups. Conclusion: The CM derived from human BM-MSCs has the capacity to rescue oxidatively damaged human TM cells associated with decreased autophagy and apoptosis. The BM-MSCs CM has potential for slowing down age- and disease-related degeneration of TM in patients with glaucoma, facilitating success in the control of IOP. |
| first_indexed | 2024-04-10T04:21:49Z |
| format | Article |
| id | doaj.art-814f12f486474c1b9c6729058134c625 |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2024-04-10T04:21:49Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-814f12f486474c1b9c6729058134c6252023-03-11T04:19:57ZengElsevierRegenerative Therapy2352-32042023-03-01225058Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cellsYu-Fan Chang0Yung-Hsin Cheng1Yu-Chieh Ko2Shih-Hwa Chiou3Catherine Jui-Ling Liu4Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, TaiwanDepartment of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, TaiwanNational Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, TaiwanInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; Corresponding author. Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, Department of Medical Research, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District, Taipei, 112, Taiwan, ROC. Fax: +886-2-28757133.National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; Corresponding author. National Yang Ming Chiao Tung University School of Medicine, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan, ROC, Department of Ophthalmology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District, Taipei, 112, Taiwan, ROC. Fax: +886-2-28757133.Introduction: Glaucoma is a vision-threatening disease associated with accelerated aging of trabecular meshwork (TM) which results in elevated intraocular pressure (IOP). Increased oxidative stress in TM plays an important role in cellular molecular damage which leads to senescence. Autophagy is an intracellular lysosomal degradation process which is activated when cells are under stressful condition, and emerging studies have demonstrated increased expression of modulators of apoptosis and expression of autophagic cascade in ex-vivo TM specimens or cultured TM cells under oxidative stress. Recently, studies have shown neuroprotective and IOP-lowering effects after transplanting mesenchymal stem cells (MSCs) or injecting condition medium (CM) of MSCs into ocular hypertension animal models. However, knowledge of the underlying mechanism accounting for these effects is limited. Using condition medium (CM) from human bone marrow-derived mesenchymal stem cells (BM-MSCs), we investigated the effects of the CM derived from BM-MSCs on TM autophagy and apoptosis. Methods: H2O2 was added to culture medium of human TM cells to mimic oxidative damage in glaucomatous eyes, and the autophagic and anti-apoptotic effects of BM-MSCs-derived CM was explored on the oxidatively damaged cells. Mitochondrial ROS production was examined by MitoSOX™, apoptosis was evaluated using terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) staining, and the expression of proteins involved in autophagy as well as extracellular matrix was investigated via Western blot. Results: There were no significant differences in TM cell viability when the cells were treated with different concentrations of CM in the absence of oxidative stress. Cell viability was significantly higher in oxidatively damaged TM cells treated with 1X or 5X CM compared to untreated TM cells under oxidative stress. The mitochondrial ROS level significantly increased with oxidative stress, which was mitigated in the CM treatment groups. DNA fragmentation significantly decreased in oxidatively stressed TM cells after treatment with CM. LCB3 II/LCB3 I was significantly elevated in the oxidative stress group compared to the control group and was significantly decreased in the CM treatment groups. Expression of fibronectin was not significantly different among the groups. Conclusion: The CM derived from human BM-MSCs has the capacity to rescue oxidatively damaged human TM cells associated with decreased autophagy and apoptosis. The BM-MSCs CM has potential for slowing down age- and disease-related degeneration of TM in patients with glaucoma, facilitating success in the control of IOP.http://www.sciencedirect.com/science/article/pii/S2352320422001249Mesenchymal stem cellApoptosisAutophagyTrabecular meshwork cell |
| spellingShingle | Yu-Fan Chang Yung-Hsin Cheng Yu-Chieh Ko Shih-Hwa Chiou Catherine Jui-Ling Liu Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells Regenerative Therapy Mesenchymal stem cell Apoptosis Autophagy Trabecular meshwork cell |
| title | Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells |
| title_full | Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells |
| title_fullStr | Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells |
| title_full_unstemmed | Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells |
| title_short | Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells |
| title_sort | anti apoptotic and autophagic effect using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells |
| topic | Mesenchymal stem cell Apoptosis Autophagy Trabecular meshwork cell |
| url | http://www.sciencedirect.com/science/article/pii/S2352320422001249 |
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