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She JW, Young CM, Chou SJ, Wu YR, Lin YT, Huang TY, Shen MY, Chen CY, Yang YP, Chien Y, Ayalew H, Liao WH, Tung YC, Shyue JJ, Chiou SH, Yu HH. Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells. Biomaterials 2025; 313:122770. [PMID: 39226653 DOI: 10.1016/j.biomaterials.2024.122770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 07/30/2024] [Accepted: 08/21/2024] [Indexed: 09/05/2024]
Abstract
Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.
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Affiliation(s)
- Jia-Wei She
- Smart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan; Taiwan International Graduate Program (TIGP), Nano Science & Technology Program, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan; Department of Engineering and System Science, National Tsing Hua University, No. 101, Section 2, Guangfu Road, East District, 300, Hsinchu City, Taiwan
| | - Chia-Mei Young
- Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, 11217, Taiwan
| | - Shih-Jie Chou
- Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, 11217, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, 11217, Taiwan
| | - You-Ren Wu
- Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, 11217, Taiwan
| | - Yu-Ting Lin
- Smart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan
| | - Tzu-Yang Huang
- Smart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan
| | - Mo-Yuan Shen
- Smart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan
| | - Chih-Ying Chen
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, 11217, Taiwan
| | - Yi-Ping Yang
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, 11217, Taiwan
| | - Yueh Chien
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, 11217, Taiwan
| | - Hailemichael Ayalew
- Smart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan
| | - Wei-Hao Liao
- Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan
| | - Yi-Chung Tung
- Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan
| | - Jing-Jong Shyue
- Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan
| | - Shih-Hwa Chiou
- Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, 11217, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, 11217, Taiwan; Genomic Research Center, Academia Sinica, Taipei, 11529, Taiwan.
| | - Hsiao-Hua Yu
- Smart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan.
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Namdari M, McDonnell FS. Extracellular vesicles as emerging players in glaucoma: Mechanisms, biomarkers, and therapeutic targets. Vision Res 2025; 226:108522. [PMID: 39581065 PMCID: PMC11640964 DOI: 10.1016/j.visres.2024.108522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 11/05/2024] [Accepted: 11/07/2024] [Indexed: 11/26/2024]
Abstract
In recent years, extracellular vesicles (EVs) have attracted significant scientific interest due to their widespread distribution, their potential as disease biomarkers, and their promising applications in therapy. Encapsulated by lipid bilayers these nanovesicles include small extracellular vesicles (sEV) (30-150 nm), microvesicles (100-1000 nm), and apoptotic bodies (100-5000 nm) and are essential for cellular communication, immune responses, biomolecular transport, and physiological regulation. As they reflect the condition and functionality of their originating cells, EVs play critical roles in numerous physiological processes and diseases. Therefore, EVs offer valuable opportunities for uncovering disease mechanisms, enhancing drug delivery systems, and identifying novel biomarkers. In the context of glaucoma, a leading cause of irreversible blindness, the specific roles of EVs are still largely unexplored. This review examines the emerging role of EVs in the pathogenesis of glaucoma, with a focus on their potential as diagnostic biomarkers and therapeutic agents. Through a thorough analysis of current literature, we summarize key advancements in EV research and identify areas where further investigation is needed to fully understand their function in glaucoma.
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Affiliation(s)
- Maral Namdari
- John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA
| | - Fiona S McDonnell
- John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA; Biomedical Engineering, University of Utah, Salt Lake City, UT, USA; Pharmacology and Toxicology, University of Utah Salt Lake City, UT, USA.
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Sen S, de Guimaraes TAC, Filho AG, Fabozzi L, Pearson RA, Michaelides M. Stem cell-based therapies for retinal diseases: focus on clinical trials and future prospects. Ophthalmic Genet 2024:1-14. [PMID: 39544140 DOI: 10.1080/13816810.2024.2423784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 10/09/2024] [Accepted: 10/26/2024] [Indexed: 11/17/2024]
Abstract
Stem cell-based therapy has gained importance over the past decades due to huge advances in science and technology behind the generation and directed differentiation of pluripotent cells from embryos and adult cells. Preclinical proof-of-concept studies have been followed by clinical trials showing efficacy and safety of transplantation of stem cell-based therapy, which are beginning to establish this as a modality of treatment. Disease candidates of interest are primarily conditions that may benefit from replacing dead or dying cells, including advanced inherited retinal dystrophies and age-related macular degeneration, and predominantly seek to transplant either RPE or photoreceptors, although neurotrophic approaches have also been trialed. Whilst a consensus has yet to be reached about the best stage/type of cells for transplantation (stem cells, progenitor cells, differentiated RPE and photoreceptors) and the methods of implantation (sheet, suspension), several CTs have shown safety. There remain potential concerns regarding tumorigenicity and immune rejection; however, with ongoing improvements in cell generation, selection, and delivery, these can be minimized. Earlier studies showed efficacy with immunosuppressive drugs to prevent rejection, and recent donor-matched transplants have avoided the need for immunosuppression. Retinal regenerative medicine is a challenging field and is in a nascent stage but holds tremendous promise. This narrative review delves into the current understanding of stem cells and the latest clinical trials of retinal cell transplantation.
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Affiliation(s)
- Sagnik Sen
- Deaprtment of Genetics, Moorfields Eye Hospital, London, UK
- UCL Institute of Ophthalmology, University College London, London, UK
| | | | | | | | - Rachael A Pearson
- Ocular Cell and Gene Therapy Group, Centre for Gene Therapy and Regenerative Medicine, King's College London, London, UK
| | - Michel Michaelides
- Deaprtment of Genetics, Moorfields Eye Hospital, London, UK
- UCL Institute of Ophthalmology, University College London, London, UK
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Rong L, Wei W, Fang Y, Liu Y, Gao T, Wang L, Hao J, Gu X, Wu J, Wu W. Clinical-grade human embryonic stem cell-derived mesenchymal stromal cells ameliorate diabetic retinopathy in db/db mice. Cytotherapy 2024; 26:606-615. [PMID: 38483364 DOI: 10.1016/j.jcyt.2024.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 02/25/2024] [Accepted: 02/26/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND AIMS Mesenchymal stromal cells (MSCs) hold great promise in the treatment of diabetic retinopathy (DR), as evidenced by increasing preclinical and clinical studies. However, the absence of standardized and industrialized clinical-grade donor cells hampers the continued development and large-scale clinical application of MSCs-based therapies for DR. Previously, we have identified a unique population of MSCs generated from a clinical-grade human embryonic stem cell (hESC) line under Good Manufacturing Practice conditions that could be a potential source to address the issues. Here, we investigated the therapeutic potential of the clinical-grade hESC line-derived MSCs (hESC-MSCs) on db/db mice with DR. METHODS hESC-MSCs were initially characterized by morphological assessment, flow cytometry analysis and trilineage differentiation assays. These cells (5 × 106 cells) were then transplanted intravenously into 12-week-old db/db mice via tail vein, with phosphate-buffered saline transplantation and untreated groups used as controls. The retinal alterations in neural functions and microvascular perfusions, and inflammatory responses in peripheral blood and retina were evaluated at 4 and 6 weeks after transplantation using electroretinography, optical coherence tomography angiography and flow cytometry, respectively. Body weight and fasting blood glucose (FBG) levels were also measured to investigate their systemic implications. RESULTS Compared with controls, intravenous transplantation of hESC-MSCs could significantly: (i) enhance impaired retinal electroretinography functions (including amplitudes of a-, b-wave and oscillatory potentials) at 4 weeks after transplantation; (ii) alleviate microvascular dysfunctions, especially in the inner retina with significance (including reducing non-perfusion area and increasing vascular area density) at 4 weeks after transplantation; (iii) decrease FBG levels at 4 weeks after transplantation and induce weight loss up to 6 weeks after transplantation and (iv) increase both peripheral blood and retinal interleukin-10 levels at 4 weeks after transplantation and modulate peripheral blood inflammatory cytokines and chemokines levels, such as monocyte chemotactic protein-1, up to 6 weeks after transplantation. CONCLUSIONS The findings of our study indicated that intravenous transplantation of hESC-MSCs ameliorated retinal neural and microvascular dysfunctions, regulated body weight and FBG and modulated peripheral blood and retinal inflammation responses in a mouse model of DR. These results suggest that hESC-MSCs could be a potentially effective clinical-grade cell source for the treatment of DR.
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Affiliation(s)
- Liyuan Rong
- Senior Department of Ophthalmology, 3rd Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wumei Wei
- State Key Laboratory of Stem Cell and Reproductive Biology, National Stem Cell Resource Center, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
| | - Yifan Fang
- Senior Department of Ophthalmology, 3rd Medical Center of Chinese PLA General Hospital, Beijing, China; Airforce Hospital of Southern Theater Command, Guangzhou, China
| | - Yanchen Liu
- Department of Ophthalmology, Yidu Central Hospital Affiliated to Weifang Medical University, Weifang, China
| | - Tingting Gao
- State Key Laboratory of Stem Cell and Reproductive Biology, National Stem Cell Resource Center, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Liu Wang
- State Key Laboratory of Stem Cell and Reproductive Biology, National Stem Cell Resource Center, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Department of Ophthalmology, Yidu Central Hospital Affiliated to Weifang Medical University, Weifang, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Jie Hao
- State Key Laboratory of Stem Cell and Reproductive Biology, National Stem Cell Resource Center, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Xianliang Gu
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jun Wu
- State Key Laboratory of Stem Cell and Reproductive Biology, National Stem Cell Resource Center, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
| | - Wei Wu
- Senior Department of Ophthalmology, 3rd Medical Center of Chinese PLA General Hospital, Beijing, China.
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Tang Q, Buonfiglio F, Böhm EW, Zhang L, Pfeiffer N, Korb CA, Gericke A. Diabetic Retinopathy: New Treatment Approaches Targeting Redox and Immune Mechanisms. Antioxidants (Basel) 2024; 13:594. [PMID: 38790699 PMCID: PMC11117924 DOI: 10.3390/antiox13050594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/06/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-β inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways.
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Affiliation(s)
- Qi Tang
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; (F.B.); (E.W.B.); (L.Z.); (N.P.); (C.A.K.)
| | | | | | | | | | | | - Adrian Gericke
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; (F.B.); (E.W.B.); (L.Z.); (N.P.); (C.A.K.)
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Poojari AS, Wairkar S, Kulkarni YA. Stem cells as a regenerative medicine approach in treatment of microvascular diabetic complications. Tissue Cell 2023; 85:102225. [PMID: 37801960 DOI: 10.1016/j.tice.2023.102225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 09/20/2023] [Accepted: 09/20/2023] [Indexed: 10/08/2023]
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by high blood glucose and is associated with high morbidity and mortality among the diabetic population. Uncontrolled chronic hyperglycaemia causes increased formation and accumulation of different oxidative and nitrosative stress markers, resulting in microvascular and macrovascular complications, which might seriously affect the quality of a patient's life. Conventional treatment strategies are confined to controlling blood glucose by regulating the insulin level and are not involved in attenuating the life-threatening complications of diabetes mellitus. Thus, there is an unmet need to develop a viable treatment strategy that could target the multi-etiological factors involved in the pathogenesis of diabetic complications. Stem cell therapy, a regenerative medicine approach, has been investigated in diabetic complications owing to their unique characteristic features of self-renewal, multilineage differentiation and regeneration potential. The present review is focused on potential therapeutic applications of stem cells in the treatment of microvascular diabetic complications such as nephropathy, retinopathy, and polyneuropathy.
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Affiliation(s)
- Avinash S Poojari
- Shobhabhen Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India
| | - Sarika Wairkar
- Shobhabhen Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India
| | - Yogesh A Kulkarni
- Shobhabhen Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India.
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Gacche RN. Changing landscape of anti-angiogenic therapy: Novel approaches and clinical perspectives. Biochim Biophys Acta Rev Cancer 2023; 1878:189020. [PMID: 37951481 DOI: 10.1016/j.bbcan.2023.189020] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/03/2023] [Accepted: 11/04/2023] [Indexed: 11/14/2023]
Abstract
Targeting angiogenesis has remained one of the important aspects in disease biology in general and cancer in particular. Currently (June 2023), over 593 clinical trials have been registered at ClinicalTrials.gov having inference of term 'angiogenesis'. A panel of 14 anti-angiogenic drugs have been approved by FDA for the treatment of variety of cancers and other human ailments. Although the anti-angiogenic therapy (AAT) has gained significant clinical attention as a promising approach in the treatment of various diseases, particularly cancer, however, sizable literature has accumulated in the recent past describing the aggressive nature of tumours after the drug holidays, evolving drug resistance and off-target toxicities. Nevertheless, the emergence of inscrutable compensatory or alternative angiogenic mechanisms is limiting the efficacy of anti-angiogenic drugs and focussing the therapeutic regime as a puzzle of 'Lernaean hydra'. This review offers an overview of recent updates on the efficacy of antiangiogenic therapy and the current clinical performance of aaRTK inhibitors. Additionally, it also explores the changing application landscape of AAT, focusing on its role in diabetic nephropathy, age-related macular degeneration and other neovascular ocular disorders. Combination therapy with antiangiogenic drugs and immune check point inhibitors (ICIs) has emerged as a potential strategy to enhance the therapeutic index of cancer immunotherapy. While clinical studies have demonstrated the clinical efficacy of this approach, they also highlight the complex and sometimes unpredictable adverse events associated with it. Normalizing tumour vasculature has been identified as a key factor in unlocking the full potential of ICIs, thereby providing hope for improved treatment outcomes. The future prospects and challenges of AAT have been described with special reference to integration of technological advances for enhancing its efficacy and applications beyond its discovery.
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Affiliation(s)
- Rajesh N Gacche
- Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, MS, India.
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Kim H, Goh YS, Park SE, Hwang J, Kang N, Jung JS, Kim YB, Choi EK, Park KM. Preventive Effects of Exosome-Rich Conditioned Medium From Amniotic Membrane-Derived Mesenchymal Stem Cells for Diabetic Retinopathy in Rats. Transl Vis Sci Technol 2023; 12:18. [PMID: 37610767 PMCID: PMC10461646 DOI: 10.1167/tvst.12.8.18] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 07/22/2023] [Indexed: 08/24/2023] Open
Abstract
PURPOSE Diabetic retinopathy (DR) is an important disease that causes vision loss in many diabetic patients. Stem cell therapy has been attempted for treatment of this disease; however, it has some limitations. This study aimed to evaluate the preventive efficacy of exosome-rich conditioned medium (ERCM) derived from amniotic membrane stem cells for DR in rats. METHODS Twenty-eight 8-week-old male Sprague-Dawley rats were divided into three groups: group 1, normal control (Con) group; group 2, diabetes mellitus (DM) group; and group 3, DM with ERCM-treated (DM-ERCM) group. DM was induced by intraperitoneal injection of streptozotocin. The DM-ERCM group received ERCM containing 1.2 × 10⁹ exosomes into subconjunctival a total of four times every 2 weeks. RESULTS On electroretinogram, the DM-ERCM group had significantly higher b-wave and flicker amplitudes than those in the DM group. In fundoscopy, retinal vascular attenuation was found in both the DM and DM-ERCM groups; however, was more severe in the DM group. On histology, the ganglion cell and nerve fiber layer rates of the total retinal layer significantly increased in the DM group compared with the Con group, whereas the DM-ERCM group showed no significant difference compared with the Con group. Cataracts progressed significantly more in the DM group than that in the DM-ERCM group and there was no uveitis in the DM-ERCM group. CONCLUSIONS Subconjunctival ERCM delayed the progression of DR and cataracts and significantly reduced the incidence of uveitis. TRANSLATIONAL RELEVANCE Our study shows the clinical potential of minimally invasive exosome-rich conditioned medium treatment to prevent diabetic retinopathy.
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Affiliation(s)
- Hyemin Kim
- Laboratory of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
| | - Yeong-Seok Goh
- Laboratory of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
| | - Sang-Eun Park
- Laboratory of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
| | - Jiyi Hwang
- Laboratory of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
| | - Nanyoung Kang
- Laboratory of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
| | - Ji Seung Jung
- Laboratory of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
| | - Yun-Bae Kim
- Laboratory of Toxicology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
- Central Research Institute, Designed Cells Co., Ltd., Cheongju, Korea
| | - Ehn-Kyoung Choi
- Central Research Institute, Designed Cells Co., Ltd., Cheongju, Korea
| | - Kyung-Mee Park
- Laboratory of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
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Lee D, Hong HS. Substance P Alleviates Retinal Pigment Epithelium Dysfunction Caused by High Glucose-Induced Stress. Life (Basel) 2023; 13:life13051070. [PMID: 37240715 DOI: 10.3390/life13051070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 04/21/2023] [Indexed: 05/28/2023] Open
Abstract
When the retina is constantly affected by high glucose (HG) due to diabetes, the barrier function of the retinal pigment epithelium (RPE) is impaired, accompanied by unnecessary vascularization. This eventually leads to the development of diabetic retinopathy (DR). This study investigated the recovery effect of substance P (SP) on RPE injured by HG. RPE was treated with HG for 24 h, and HG-induced cellular injuries were confirmed. SP was added to the dysfunctional RPE. Compared to RPE in low glucose (LG) conditions, HG-damaged RPE had large, fibrotic cell shapes, and its cellular viability decreased. HG treatment reduced tight junction protein expression levels and caused oxidative stress by interrupting the antioxidant system; this was followed by inflammatory factor intracellular adhesion molecule-1 (ICAM-1), Monocyte chemotactic protein-1 (MCP-1), and angiogenesis factor vascular endothelial growth factor (VEGF) expression. SP treatment contributed to RPE recovery by enhancing cell viability, tight junction protein expression, and RPE function under HG conditions, possibly by activating the Akt signaling pathway. Importantly, SP treatment reduced ICAM-1, MCP-1, and VEGF expression. Collectively, SP activated survival signals to suppress oxidative stress and improve retinal barrier function in RPE, accompanied by immune suppression. This suggests the possible application of SP to diabetic retinal injuries.
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Affiliation(s)
- Dahyeon Lee
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Hyun Sook Hong
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
- East-West Medical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea
- Kyung Hee Institute of Regenerative Medicine (KIRM), Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea
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Xiao H, Tang J, Zhang F, Liu L, Zhou J, Chen M, Li M, Wu X, Nie Y, Duan J. Global trends and performances in diabetic retinopathy studies: A bibliometric analysis. Front Public Health 2023; 11:1128008. [PMID: 37124794 PMCID: PMC10136779 DOI: 10.3389/fpubh.2023.1128008] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 03/09/2023] [Indexed: 05/02/2023] Open
Abstract
Objective The objective of this study is to conduct a comprehensive bibliometric analysis to identify and evaluate global trends in diabetic retinopathy (DR) research and visualize the focus and frontiers of this field. Methods Diabetic retinopathy-related publications from the establishment of the Web of Science (WOS) through 1 November 2022 were retrieved for qualitative and quantitative analyses. This study analyzed annual publication counts, prolific countries, institutions, journals, and the top 10 most cited literature. The findings were presented through descriptive statistics. VOSviewer 1.6.17 was used to exhibit keywords with high frequency and national cooperation networks, while CiteSpace 5.5.R2 displayed the timeline and burst keywords for each term. Results A total of 10,709 references were analyzed, and the number of publications continuously increased over the investigated period. America had the highest h-index and citation frequency, contributing to the most influence. China was the most prolific country, producing 3,168 articles. The University of London had the highest productivity. The top three productive journals were from America, and Investigative Ophthalmology Visual Science had the highest number of publications. The article from Gulshan et al. (2016; co-citation counts, 2,897) served as the representative and symbolic reference. The main research topics in this area were incidence, pathogenesis, treatment, and artificial intelligence (AI). Deep learning, models, biomarkers, and optical coherence tomography angiography (OCTA) of DR were frontier hotspots. Conclusion Bibliometric analysis in this study provided valuable insights into global trends in DR research frontiers. Four key study directions and three research frontiers were extracted from the extensive DR-related literature. As the incidence of DR continues to increase, DR prevention and treatment have become a pressing public health concern and a significant area of research interest. In addition, the development of AI technologies and telemedicine has emerged as promising research frontiers for balancing the number of doctors and patients.
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Affiliation(s)
- Huan Xiao
- School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinfan Tang
- School of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Feng Zhang
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Luping Liu
- School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jing Zhou
- School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Meiqi Chen
- School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mengyue Li
- School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaoxiao Wu
- School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yingying Nie
- School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Junguo Duan
- School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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11
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Saha B, Roy A, Beltramo E, Sahoo OS. Stem cells and diabetic retinopathy: From models to treatment. Mol Biol Rep 2023; 50:4517-4526. [PMID: 36842153 DOI: 10.1007/s11033-023-08337-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 02/15/2023] [Indexed: 02/27/2023]
Abstract
Diabetic retinopathy is a common yet complex microvascular disease, caused as a complication of diabetes mellitus. Associated with hyperglycemia and subsequent metabolic abnormalities, advanced stages of the disease lead to fibrosis, subsequent visual impairment and blindness. Though clinical postmortems, animal and cell models provide information about the progression and prognosis of diabetic retinopathy, its underlying pathophysiology still needs a better understanding. In addition to it, the loss of pericytes, immature retinal angiogenesis and neuronal apoptosis portray the disease treatment to be challenging. Indulged with cell loss of both vascular and neuronal type cells, novel therapies like cell replacement strategies by various types of stem cells have been sightseen as a possible treatment of the disease. This review provides insight into the pathophysiology of diabetic retinopathy, current models used in modelling the disease, as well as the varied aspects of stem cells in generating three-dimensional retinal models. Further outlook on stem cell therapy and the future directions of stem cell treatment in diabetic retinopathy have also been contemplated.
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Affiliation(s)
- Bihan Saha
- National Institute of Technology Durgapur, Durgapur, 713209, West Bengal, India
| | - Akshita Roy
- Autonomous State Medical College, Fatehpur, 212601, Uttar Pradesh, India
| | - Elena Beltramo
- Department of Medical Sciences, University of Turin, 10124, Turin, Italy
| | - Om Saswat Sahoo
- National Institute of Technology Durgapur, Durgapur, 713209, West Bengal, India.
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Musa M, Zeppieri M, Enaholo ES, Salati C, Parodi PC. Adipose Stem Cells in Modern-Day Ophthalmology. Clin Pract 2023; 13:230-245. [PMID: 36826163 PMCID: PMC9955457 DOI: 10.3390/clinpract13010021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/30/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
Stem cells (SCs) have evolved as an interesting and viable factor in ophthalmologic patient care in the past decades. SCs have been classified as either embryonic, mesenchymal, tissue-specific, or induced pluripotent cells. Multiple novel management techniques and clinical trials have been established to date. While available publications are predominantly animal-model-based, significant material is derived from human studies and case-selected scenarios. This possibility of explanting cells from viable tissue to regenerate/repair damaged tissue points to an exciting future of therapeutic options in all fields of medicine, and ophthalmology is surely not left out. Adipose tissue obtained from lipo-aspirates has been shown to produce mesenchymal SCs that are potentially useful in different body parts, including the oculo-visual system. An overview of the anatomy, physiology, and extraction process for adipose-tissue-derived stem cells (ADSC) is important for better understanding the potential therapeutic benefits. This review examines published data on ADSCs in immune-modulatory, therapeutic, and regenerative treatments. We also look at the future of ADSC applications for ophthalmic patient care. The adverse effects of this relatively novel therapy are also discussed.
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Affiliation(s)
- Mutali Musa
- Department of Optometry, University of Benin, Benin City 300238, Nigeria
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy
| | | | - Carlo Salati
- Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy
| | - Pier Camillo Parodi
- Department of Plastic Surgery, University Hospital of Udine, 33100 Udine, Italy
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13
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Ma Y, DU Y, Xu Q, Bao H, Liu Z, Li Y, Liu W. Inhibiting MiR-34α reduces retinal cell apoptosis and downstream NF-κB pathway in diabetic retinopathy rats through regulating HMGB1 expression. Minerva Med 2023; 114:49-55. [PMID: 32683849 DOI: 10.23736/s0026-4806.20.06625-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND This is a research aimed to study the effect of micro ribonucleic acid (miR)-34α on the retinal cell apoptosis in diabetic retinopathy (DR) rats and its key molecular mechanism. METHODS Sprague-Dawley rats were randomly divided into healthy group (H group, N.=5), diabetes group (D group, N.=5), diabetes + negative control transfection group (N group, N.=5) and diabetes + miR-34α inhibitor transfection group (M group, N.=5). The rat model of diabetes was established via intraperitoneal injection of 2% streptozotocin solution (60 mg/kg). After 72 h, the urine glucose and blood glucose were detected, and the urine glucose above 3+ and the blood glucose concentration >16.7 mmol/L indicated the successful modeling. After the rats were normally fed for 4 months, the changes in expression of miR-34α in retinal tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR), the pathological changes in retinal tissues were observed via hematoxylin-eosin (HE) staining, and the retinal cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the changes in the number of cells containing active caspase-3 in retinal tissues were determined through immunohistochemistry, and the changes in expressions of caspase-3, high mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) in retinal tissues were determined through Western blotting. RESULTS Compared with those in H group, the cell density declined, and the cells were arranged disorderly with swelling in each retinal layer, the expression of miR-34α in retinal tissues was increased, the retinal cell apoptosis was enhanced, the number of cells containing active caspase-3 in retinal tissues rose, and the expressions of caspase-3, HMGB1 and NF-κB in retinal tissues were increased in D group, N group and M group (P<0.05). Compared with those in D group and N group, the cell density rose, and the cells were arranged less disorderly with milder swelling in each retinal layer, the expression of miR-34α in retinal tissues declined, the retinal cell apoptosis was weakened, the number of cells containing active caspase-3 in retinal tissues was decreased, and the expressions of caspase-3, HMGB1 and NF-κB in retinal tissues were reduced in M group (P<0.05). CONCLUSIONS Inhibiting miR-34α reduces the retinal cell apoptosis in DR rats through regulating the HMGB1 expression and downstream NF-κB pathway.
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Affiliation(s)
- Yibin Ma
- Department of Ophthalmology, Taian City Central Hospital, Taian, China
| | - Yunhong DU
- Department of Ophthalmology, Taian City Central Hospital, Taian, China
| | - Qian Xu
- Department of Ophthalmology, Taian City Central Hospital, Taian, China
| | - Huijing Bao
- Department of Ophthalmology, Taian City Central Hospital, Taian, China
| | - Zhonglian Liu
- Radiotherapy Center, Taian Oncology Hospital, Taian, China
| | - Yingchao Li
- Department of Ophthalmology, Taian City Central Hospital, Taian, China
| | - Wenjing Liu
- Department of Ophthalmology, Taian City Central Hospital, Taian, China -
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14
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Miotti G, Parodi PC, Ferrari A, Salati C, Zeppieri M. Stem Cells in Ophthalmology: From the Bench to the Bedside. HANDBOOK OF STEM CELL APPLICATIONS 2023:1-24. [DOI: 10.1007/978-981-99-0846-2_10-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 03/22/2023] [Indexed: 09/13/2023]
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15
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Miotti G, Parodi PC, Ferrari A, Salati C, Zeppieri M. Stem Cells in Ophthalmology: From the Bench to the Bedside. HANDBOOK OF STEM CELL APPLICATIONS 2023:1-24. [DOI: https:/doi.org/10.1007/978-981-99-0846-2_10-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 03/22/2023] [Indexed: 08/28/2023]
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16
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Zhou L, Zhang H, Wu S, He Y, Guo K. In vitro induction and intraocular application in oxygen-induced retinopathy of adipose-derived mesenchymal stem cells. Mol Vis 2022; 28:432-440. [PMID: 36601410 PMCID: PMC9767843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 12/19/2022] [Indexed: 01/06/2023] Open
Abstract
Purpose We designed a study to find theoretical evidence for the induction, movement, fusion, proliferation, and safety of human adipose mesenchymal stem cells (hADSCs) in intraocular application. Methods HADSCs were induced to confirm that they can express the characteristics of endothelial cells (ECs) in vitro. HADSCs were intraocularly injected into oxygen-induced retinopathy (OIR) mice to check the movement, fusion, proliferation, and prognosis in vivo. Electron microscopy was used to check retinal changes to confirm the safety of hADSCs in intraocular application. Results After induction, hADSCs expressed von Willebrand Factor (vWF), the cell marker of ECs. The hADSCs were distributed above the retina after an intravitreal injection in the OIR mice. The injected cells did not fuse with the retina and gathered in the central and peripheral areas, which is the lesion area of the OIR model. Five days after the hADSC intravitreal injection, the area of neovascularization was reduced by 94.83% compared with that of the OIR group. Hematologic staining and electron microscopy did not show noticeable proliferation and degeneration of the retina. Conclusions This study provides evidence for the intraocular application of hADSCs.
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Affiliation(s)
- Lvlv Zhou
- Department of Ophthalmology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haifeng Zhang
- Department of Physiology, Inner Mongolia Medical University, Inner Mongolia, China
| | - Sarina Wu
- Inner Mongolia Institute of Traditional Chinese Medicine, Inner Mongolia Medical University, Inner Mongolia, China
| | - Yuhong He
- Department of Ophthalmology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, China
| | - Kai Guo
- Department of Ophthalmology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, China
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17
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Anand S, Trounce IA, Gangoda L. Role of extracellular vesicles in mitochondrial eye diseases. IUBMB Life 2022; 74:1264-1272. [PMID: 36308309 PMCID: PMC10947567 DOI: 10.1002/iub.2687] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/14/2022] [Indexed: 03/20/2024]
Abstract
Extracellular vesicles (EVs) are small packages that are released by almost all types of cells. While the role of EVs in pathogenesis of certain diseases such as cancer is well established, EVs role in ocular health and disease is still at early stages of investigation. Given the significant role of EVs in pathological development and progression of diseases such as cancer, EVs present a similar opportunity for investigation in ocular pathophysiology. Studies have shown the presence of EVs in fluids from the ocular environment have close links with ocular health and disease. Hence, the cargo carried in EVs from ocular fluids can be used for monitoring disease phenotypes or therapeutic outcomes in eye-related disorders. Furthermore, in recent times EVs have increasingly gained attention as therapeutics and drug-delivery vehicles for treatment of eye diseases. There is a close relationship between EVs and mitochondria functioning with mitochondria dysfunction leading to a significant number of ophthalmic disorders. This review discusses the current knowledge of EVs in visual systems with a special focus on eye diseases resulting from dysfunctional mitochondria.
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Affiliation(s)
- Sushma Anand
- Centre for Eye Research AustraliaRoyal Victorian Eye and Ear HospitalEast MelbourneVictoriaAustralia
- Opthalmology, Department of SurgeryUniversity of MelbourneMelbourneVictoriaAustralia
| | - Ian A. Trounce
- Centre for Eye Research AustraliaRoyal Victorian Eye and Ear HospitalEast MelbourneVictoriaAustralia
- Opthalmology, Department of SurgeryUniversity of MelbourneMelbourneVictoriaAustralia
| | - Lahiru Gangoda
- Centre for Eye Research AustraliaRoyal Victorian Eye and Ear HospitalEast MelbourneVictoriaAustralia
- Opthalmology, Department of SurgeryUniversity of MelbourneMelbourneVictoriaAustralia
- The Walter and Eliza Hall Institute of Medical Research (WEHI)MelbourneVictoriaAustralia
- Department of Medical BiologyUniversity of MelbourneMelbourneVictoriaAustralia
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18
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Chen X, Jiang Y, Duan Y, Zhang X, Li X. Mesenchymal-Stem-Cell-Based Strategies for Retinal Diseases. Genes (Basel) 2022; 13:genes13101901. [PMID: 36292786 PMCID: PMC9602395 DOI: 10.3390/genes13101901] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 10/08/2022] [Accepted: 10/11/2022] [Indexed: 12/04/2022] Open
Abstract
Retinal diseases are major causes of irreversible vision loss and blindness. Despite extensive research into their pathophysiology and etiology, pharmacotherapy effectiveness and surgical outcomes remain poor. Based largely on numerous preclinical studies, administration of mesenchymal stem cells (MSCs) as a therapeutic strategy for retinal diseases holds great promise, and various approaches have been applied to the therapies. However, hindered by the retinal barriers, the initial vision for the stem cell replacement strategy fails to achieve the anticipated effect and has now been questioned. Accumulating evidence now suggests that the paracrine effect may play a dominant role in MSC-based treatment, and MSC-derived extracellular vesicles emerge as a novel compelling alternative for cell-free therapy. This review summarizes the therapeutic potential and current strategies of this fascinating class of cells in retinal degeneration and other retinal dysfunctions.
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Lechner J, Medina RJ, Lois N, Stitt AW. Advances in cell therapies using stem cells/progenitors as a novel approach for neurovascular repair of the diabetic retina. Stem Cell Res Ther 2022; 13:388. [PMID: 35907890 PMCID: PMC9338609 DOI: 10.1186/s13287-022-03073-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 07/20/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Diabetic retinopathy, a major complication of diabetes mellitus, is a leading cause of sigh-loss in working age adults. Progressive loss of integrity of the retinal neurovascular unit is a central element in the disease pathogenesis. Retinal ischemia and inflammatory processes drive interrelated pathologies such as blood retinal barrier disruption, fluid accumulation, gliosis, neuronal loss and/or aberrant neovascularisation. Current treatment options are somewhat limited to late-stages of the disease where there is already significant damage to the retinal architecture arising from degenerative, edematous and proliferative pathology. New preventive and interventional treatments to target early vasodegenerative and neurodegenerative stages of the disease are needed to ensure avoidance of sight-loss. MAIN BODY Historically, diabetic retinopathy has been considered a primarily microvascular disease of the retina and clinically it is classified based on the presence and severity of vascular lesions. It is now known that neurodegeneration plays a significant role during the pathogenesis. Loss of neurons has been documented at early stages in pre-clinical models as well as in individuals with diabetes and, in some, even prior to the onset of clinically overt diabetic retinopathy. Recent studies suggest that some patients have a primarily neurodegenerative phenotype. Retinal pigment epithelial cells and the choroid are also affected during the disease pathogenesis and these tissues may also need to be addressed by new regenerative treatments. Most stem cell research for diabetic retinopathy to date has focused on addressing vasculopathy. Pre-clinical and clinical studies aiming to restore damaged vasculature using vasoactive progenitors including mesenchymal stromal/stem cells, adipose stem cells, CD34+ cells, endothelial colony forming cells and induced pluripotent stem cell derived endothelial cells are discussed in this review. Stem cells that could replace dying neurons such as retinal progenitor cells, pluripotent stem cell derived photoreceptors and ganglion cells as well as Müller stem cells are also discussed. Finally, challenges of stem cell therapies relevant to diabetic retinopathy are considered. CONCLUSION Stem cell therapies hold great potential to replace dying cells during early and even late stages of diabetic retinopathy. However, due to the presence of different phenotypes, selecting the most suitable stem cell product for individual patients will be crucial for successful treatment.
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Affiliation(s)
- Judith Lechner
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast, UK.
| | - Reinhold J Medina
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast, UK
| | - Noemi Lois
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast, UK
| | - Alan W Stitt
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast, UK.
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20
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Takkar B, Sheemar A, Jayasudha R, Soni D, Narayanan R, Venkatesh P, Shivaji S, Das T. Unconventional avenues to decelerated diabetic retinopathy. Surv Ophthalmol 2022; 67:1574-1592. [PMID: 35803389 DOI: 10.1016/j.survophthal.2022.06.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 06/28/2022] [Accepted: 06/30/2022] [Indexed: 02/07/2023]
Abstract
Diabetic retinopathy (DR) is an important microvascular complication of diabetes mellitus (DM), causing significant visual impairment worldwide. Current gold standards for retarding the progress of DR include blood sugar control and regular fundus screening. Despite these measures, the incidence and prevalence of DR and vision-threatening DR remain high. Given its slowly progressive course and long latent period, opportunities to contain or slow DR before it threatens vision must be explored. This narrative review assesses the recently described unconventional strategies to retard DR progression. These include gut-ocular flow, gene therapy, mitochondrial dysfunction-oxidative stress, stem cell therapeutics, neurodegeneration, anti-inflammatory treatments, lifestyle modification, and usage of phytochemicals. These therapies impact DR directly, while some of them also influence DM control. Most of these strategies are currently in the preclinical stage, and clinical evidence remains low. Nevertheless, our review suggests that these approaches have the potential for human use to prevent the progression of DR.
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Affiliation(s)
- Brijesh Takkar
- Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India; Indian Health Outcomes, Public Health, and Economics Research (IHOPE) Centre, L V Prasad Eye Institute, Hyderabad, India.
| | - Abhishek Sheemar
- Department of Ophthalmology, All India Institute of Medical Sciences, Jodhpur, India
| | | | - Deepak Soni
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Raja Narayanan
- Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India; Indian Health Outcomes, Public Health, and Economics Research (IHOPE) Centre, L V Prasad Eye Institute, Hyderabad, India
| | - Pradeep Venkatesh
- Dr. RP Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Sisinthy Shivaji
- Prof. Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, India
| | - Taraprasad Das
- Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
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21
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Liu S, Ju Y, Gu P. Experiment-Based Interventions to Diabetic Retinopathy: Present and Advances. Int J Mol Sci 2022; 23:ijms23137005. [PMID: 35806008 PMCID: PMC9267063 DOI: 10.3390/ijms23137005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/21/2022] [Accepted: 06/22/2022] [Indexed: 02/04/2023] Open
Abstract
Diabetic retinopathy is the major blinding disease among working-age populations, which is becoming more significant due to the growth of diabetes. The metabolic-induced oxidative and inflammatory stress leads to the insult of neovascular unit, resulting in the core pathophysiology of diabetic retinopathy. Existing therapies focus on the inflammation, oxidation, and angiogenesis phenomena of diabetic retinopathy, without effect to radically cure the disease. This review also summarizes novel therapeutic attempts for diabetic retinopathy along with their advantages and disadvantages, mainly focusing on those using cellular and genetic techniques to achieve remission on a fundamental level of disease.
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Affiliation(s)
- Siwei Liu
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; (S.L.); (Y.J.)
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
| | - Yahan Ju
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; (S.L.); (Y.J.)
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
| | - Ping Gu
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; (S.L.); (Y.J.)
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
- Correspondence:
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22
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Soares MBP, Gonçalves RGJ, Vasques JF, da Silva-Junior AJ, Gubert F, Santos GC, de Santana TA, Almeida Sampaio GL, Silva DN, Dominici M, Mendez-Otero R. Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases. Front Mol Neurosci 2022; 15:883378. [PMID: 35782379 PMCID: PMC9244712 DOI: 10.3389/fnmol.2022.883378] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/19/2022] [Indexed: 11/13/2022] Open
Abstract
Neurological disorders include a wide spectrum of clinical conditions affecting the central and peripheral nervous systems. For these conditions, which affect hundreds of millions of people worldwide, generally limited or no treatments are available, and cell-based therapies have been intensively investigated in preclinical and clinical studies. Among the available cell types, mesenchymal stem/stromal cells (MSCs) have been widely studied but as yet no cell-based treatment exists for neurological disease. We review current knowledge of the therapeutic potential of MSC-based therapies for neurological diseases, as well as possible mechanisms of action that may be explored to hasten the development of new and effective treatments. We also discuss the challenges for culture conditions, quality control, and the development of potency tests, aiming to generate more efficient cell therapy products for neurological disorders.
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Affiliation(s)
- Milena B. P. Soares
- Laboratório de Engenharia Tecidual e Imunofarmacologia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (IGM-FIOCRUZ/BA), Salvador, Brazil
- Instituto SENAI de Sistemas Avançados de Saúde (CIMATEC ISI-SAS), Centro Universitário SENAI/CIMATEC, Salvador, Brazil
| | - Renata G. J. Gonçalves
- Laboratório de Neurobiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Programa Redes de Pesquisa em Saúde no Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Juliana F. Vasques
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Almir J. da Silva-Junior
- Laboratório de Neurobiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Programa Redes de Pesquisa em Nanotecnologia no Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Fernanda Gubert
- Programa Redes de Pesquisa em Saúde no Estado do Rio de Janeiro, Rio de Janeiro, Brazil
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Girlaine Café Santos
- Laboratório de Engenharia Tecidual e Imunofarmacologia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (IGM-FIOCRUZ/BA), Salvador, Brazil
- Instituto SENAI de Sistemas Avançados de Saúde (CIMATEC ISI-SAS), Centro Universitário SENAI/CIMATEC, Salvador, Brazil
| | - Thaís Alves de Santana
- Laboratório de Engenharia Tecidual e Imunofarmacologia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (IGM-FIOCRUZ/BA), Salvador, Brazil
- Instituto SENAI de Sistemas Avançados de Saúde (CIMATEC ISI-SAS), Centro Universitário SENAI/CIMATEC, Salvador, Brazil
| | - Gabriela Louise Almeida Sampaio
- Laboratório de Engenharia Tecidual e Imunofarmacologia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (IGM-FIOCRUZ/BA), Salvador, Brazil
- Instituto SENAI de Sistemas Avançados de Saúde (CIMATEC ISI-SAS), Centro Universitário SENAI/CIMATEC, Salvador, Brazil
| | | | - Massimo Dominici
- Laboratory of Cellular Therapy, Division of Oncology, University of Modena and Reggio Emilia (UNIMORE), Modena, Italy
| | - Rosalia Mendez-Otero
- Laboratório de Neurobiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Programa Redes de Pesquisa em Saúde no Estado do Rio de Janeiro, Rio de Janeiro, Brazil
- Programa Redes de Pesquisa em Nanotecnologia no Estado do Rio de Janeiro, Rio de Janeiro, Brazil
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Lokman Hakim NYDB, Noble S, Thomas NV, Geegana Gamage BS, Maxwell GK, Govindasamy V, Then KY, Das AK, Cheong SK. Genetic Modification as a New Approach to Ameliorate the Therapeutic Efficacy of Stem Cells in Diabetic Retinopathy. Eur J Ophthalmol 2022; 32:11206721211073430. [PMID: 35037488 DOI: 10.1177/11206721211073430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Over the last decades, the strategy of using stem cells has gained a lot of attention in treating many diseases. Recently, DR was identified as one of the common complications experienced by diabetic patients around the world. The current treatment strategy needs to be addressed since the active progression of DR may lead to permanent blindness. Interestingly, varieties of stem cells have emerged to optimize the therapeutic effects. It is also known that stem cells possess multilineage properties and are capable of differentiating, expanding in vitro and undergoing genetic modification. Moreover, modified stem cells have shown to be an ideal resource to prevent the degenerative disease and exhibit promising effects in conferring the migratory, anti-apoptotic, anti-inflammatory and provide better homing for cells into the damaged tissue or organ as well promoting healing properties. Therefore, the understanding of the functional properties of the stem cells may provide the comprehensive guidance to understand the manipulation of stem cells making them useful for long-term therapeutic applications. Hence in this review the potential use and current challenges of genetically modified stem cells to treat DR will be discussed along with its future perspectives.
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Affiliation(s)
| | - Steven Noble
- CryoCord Sdn Bhd, Bio-X Centre, Cyberjaya, Selangor, Malaysia
| | | | | | | | | | - Kong-Yong Then
- CryoCord Sdn Bhd, Bio-X Centre, Cyberjaya, Selangor, Malaysia
- Brighton Healthcare (Bio-X Healthcare Sdn Bhd), Bio-X Centre, Cyberjaya, Selangor, Malaysia
| | - Anjan Kumar Das
- Department of Surgery, 483702IQ City Medical College, Durgapur, West Bengal, India
| | - Soon-Keng Cheong
- Faculty of Medicine & Health Sciences, 65287Universiti Tunku Abdul Rahman (UTAR), Kajang, Selangor, Malaysia
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24
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Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases. Int J Mol Sci 2021; 23:ijms23010249. [PMID: 35008675 PMCID: PMC8745455 DOI: 10.3390/ijms23010249] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs–secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators.
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Sun F, Xu W, Qian H. The emerging role of extracellular vesicles in retinal diseases. Am J Transl Res 2021; 13:13227-13245. [PMID: 35035672 PMCID: PMC8748154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 10/14/2021] [Indexed: 06/14/2023]
Abstract
As a type of nanosized membranous vesicles secreted by living cells, extracellular vesicles (EVs) mediate intercellular communications with excellent physicochemical stability and biocompatibility. By delivering biologically active molecules including proteins, nucleic acids and lipids, EVs participate in many physiological and pathological processes. Increasing studies have suggested that EVs may be biomarkers for liquid biopsy of retinal diseases due to the ability to transfer through the blood-retinal barrier. EVs also represent a novel cell-free strategy to repair tissue damage in regenerative medicine. Evidence has indicated that EVs can be engineered and modified to enhance their efficacy. In this review, an overview of the characteristics, isolation, and identification of EVs is provided. Moreover, recent advances with EVs in the diagnosis and treatment of retinal diseases and the engineering approaches to elevate their effects are introduced, and opportunities and challenges for clinical application are discussed.
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Affiliation(s)
- Fengtian Sun
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University 301 Xuefu Road, Zhenjiang 212013, Jiangsu, China
| | - Wenrong Xu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University 301 Xuefu Road, Zhenjiang 212013, Jiangsu, China
| | - Hui Qian
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University 301 Xuefu Road, Zhenjiang 212013, Jiangsu, China
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Xu J, Zuo C. The Fate Status of Stem Cells in Diabetes and its Role in the Occurrence of Diabetic Complications. Front Mol Biosci 2021; 8:745035. [PMID: 34796200 PMCID: PMC8592901 DOI: 10.3389/fmolb.2021.745035] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 10/20/2021] [Indexed: 12/19/2022] Open
Abstract
Diabetes mellitus (DM) is becoming a growing risk factor for public health worldwide. It is a very common disease and is widely known for its susceptibility to multiple complications which do great harm to the life and health of patients, some even lead to death. To date, there are many mechanisms for the complications of diabetes, including the generation of reactive oxygen species (ROS) and the abnormal changes of gas transmitters, which ultimately lead to injuries of cells, tissues and organs. Normally, even if injured, the body can quickly repair and maintain its homeostasis. This is closely associated with the repair and regeneration ability of stem cells. However, many studies have demonstrated that stem cells happen to be damaged under DM, which may be a nonnegligible factor in the occurrence and progression of diabetic complications. Therefore, this review summarizes how diabetes causes the corresponding complications by affecting stem cells from two aspects: stem cells dysfunctions and stem cells quantity alteration. In addition, since mesenchymal stem cells (MSCs), especially bone marrow mesenchymal stem cells (BMMSCs), have the advantages of strong differentiation ability, large quantity and wide application, we mainly focus on the impact of diabetes on them. The review also puts forward the basis of using exogenous stem cells to treat diabetic complications. It is hoped that through this review, researchers can have a clearer understanding of the roles of stem cells in diabetic complications, thus promoting the process of using stem cells to treat diabetic complications.
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Affiliation(s)
- Jinyi Xu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Chengguo Zuo
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
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Saçaki CS, Mogharbel BF, Stricker PEF, Dziedzic DSM, Irioda AC, Perussolo MC, Somma AT, Montiani-Ferreira F, Moreno JCD, Dornbusch P, Sato M, Shiokawa N, de Noronha L, Nagashima S, Bacelar-Galdino M, Franco CRC, Abdelwahid E, Carvalho KAT. Potential of Human Neural Precursor Cells in Diabetic Retinopathy Therapeutics - Preclinical Model. Curr Eye Res 2021; 47:450-460. [PMID: 34749546 DOI: 10.1080/02713683.2021.2002909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Purpose: This study aimed to evaluate a cell therapy strategy with human neural precursor cells (hNPCs) to treat diabetic retinopathy (DR) in Wistar rats induced to diabetes by injecting streptozotocin. Material and methods: Wharton's Jelly Mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate to develop neurospheres and obtain the hNPCs. The animals were divided into three groups; non-diabetic (ND) n = four; diabetic without treatment (DM) n = nine; and diabetic with cell therapy (DM + hNPCs) n = nine. After eight weeks of diabetes induction and DR characteristics installed, intravitreal injection of hNPCs (1 x 106 cel/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were before and during diabetes and after cell therapy. Four weeks post-treatment, histopathological and immunohistochemistry analyses were performed. Results: The repair of the retinal structures in the treated group (DM + hNPCs) was observed by increased thickness of neuroretinal layers, especially in the ganglion cell and photoreceptor layers, higher ERG oscillatory potentials (OPs) amplitudes, and transplanted hNPCs integration into the Retinal Pigment Epithelium. Conclusions: The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regenerating the neuroretinal tissue.
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Affiliation(s)
- Claudia Sayuri Saçaki
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba, Brazil
| | - Bassam Felipe Mogharbel
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba, Brazil
| | - Priscila Elias Ferreira Stricker
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba, Brazil
| | - Dilcele Silva Moreira Dziedzic
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba, Brazil
| | - Ana Carolina Irioda
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba, Brazil
| | - Maiara Carolina Perussolo
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba, Brazil
| | - André Tavares Somma
- Veterinary Medicine Department, Federal University of Paraná, Curitiba, Brazil
| | | | | | - Peterson Dornbusch
- Veterinary Medicine Department, Federal University of Paraná, Curitiba, Brazil
| | - Mário Sato
- Ophthalmology Department, Federal University of Paraná, Curitiba, Brazil
| | - Naoye Shiokawa
- Ophthalmology Department, Federal University of Paraná, Curitiba, Brazil
| | - Lúcia de Noronha
- Pathology Laboratory of Institute of Biological and Health Sciences of Pontifical Catholic University of Paraná (PUCPR), Curitiba, Brazil
| | - Seigo Nagashima
- Pathology Laboratory of Institute of Biological and Health Sciences of Pontifical Catholic University of Paraná (PUCPR), Curitiba, Brazil
| | | | | | - Eltyeb Abdelwahid
- Feinberg School of Medicine, Feinberg Cardiovascular Research Institute,Chicago, USA
| | - Katherine Athayde Teixeirade Carvalho
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba, Brazil
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Agrawal M, Rasiah PK, Bajwa A, Rajasingh J, Gangaraju R. Mesenchymal Stem Cell Induced Foxp3(+) Tregs Suppress Effector T Cells and Protect against Retinal Ischemic Injury. Cells 2021; 10:3006. [PMID: 34831229 PMCID: PMC8616393 DOI: 10.3390/cells10113006] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/22/2021] [Accepted: 10/29/2021] [Indexed: 12/02/2022] Open
Abstract
Mesenchymal stem/stromal cells (MSC) are well known for immunomodulation; however, the mechanisms involved in their benefits in the ischemic retina are unknown. This study tested the hypothesis that MSC induces upregulation of transcription factor forkhead box protein P3 (Foxp3) in T cells to elicit immune modulation, and thus, protect against retinal damage. Induced MSCs (iMSCs) were generated by differentiating the induced pluripotent stem cells (iPSC) derived from urinary epithelial cells through a noninsertional reprogramming approach. In in-vitro cultures, iMSC transferred mitochondria to immune cells via F-actin nanotubes significantly increased oxygen consumption rate (OCR) for basal respiration and ATP production, suppressed effector T cells, and promoted differentiation of CD4+CD25+ T regulatory cells (Tregs) in coculture with mouse splenocytes. In in-vivo studies, iMSCs transplanted in ischemia-reperfusion (I/R) injured eye significantly increased Foxp3+ Tregs in the retina compared to that of saline-injected I/R eyes. Furthermore, iMSC injected I/R eyes significantly decreased retinal inflammation as evidenced by reduced gene expression of IL1β, VCAM1, LAMA5, and CCL2 and improved b-wave amplitudes compared to that of saline-injected I/R eyes. Our study demonstrates that iMSCs can transfer mitochondria to immune cells to suppress the effector T cell population. Additionally, our current data indicate that iMSC can enhance differentiation of T cells into Foxp3 Tregs in vitro and therapeutically improve the retina's immune function by upregulation of Tregs to decrease inflammation and reduce I/R injury-induced retinal degeneration in vivo.
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Affiliation(s)
- Mona Agrawal
- Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (M.A.); (P.K.R.)
| | - Pratheepa Kumari Rasiah
- Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (M.A.); (P.K.R.)
| | - Amandeep Bajwa
- James D. Eason Transplant Institute, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA;
- Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA
- Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA;
| | - Johnson Rajasingh
- Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA;
- Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Rajashekhar Gangaraju
- Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (M.A.); (P.K.R.)
- Department of Anatomy & Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
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Lysophosphatidylcholine Offsets the Protective Effects of Bone Marrow Mesenchymal Stem Cells on Inflammatory Response and Oxidative Stress Injury of Retinal Endothelial Cells via TLR4/NF- κB Signaling. J Immunol Res 2021; 2021:2389029. [PMID: 34692851 PMCID: PMC8531799 DOI: 10.1155/2021/2389029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 09/09/2021] [Accepted: 09/26/2021] [Indexed: 11/22/2022] Open
Abstract
Diabetic retinopathy (DR), as a major cause of blindness worldwide, is one common complication of diabetes mellitus. Inflammatory response and oxidative stress injury of endothelial cells play significant roles in the pathogenesis of DR. The study is aimed at investigating the effects of lysophosphatidylcholine (LPC) on the dysfunction of high glucose- (HG-) treated human retinal microvascular endothelial cells (HRMECs) after being cocultured with bone marrow mesenchymal stem cells (BMSCs) and the underlying regulatory mechanism. Coculture of BMSCs and HRMECs was performed in transwell chambers. The activities of antioxidant-related enzymes and molecules of oxidative stress injury and the contents of inflammatory cytokines were measured by ELISA. Flow cytometry analyzed the apoptosis of treated HRMECs. HRMECs were further treated with 10-50 μg/ml LPC to investigate the effect of LPC on the dysfunction of HRMECs. Western blotting was conducted to evaluate levels of TLR4 and p-NF-κB proteins. We found that BMSCs alleviated HG-induced inflammatory response and oxidative stress injury of HRMECs. Importantly, LPC offsets the protective effects of BMSCs on inflammatory response and oxidative stress injury of HRMECs. Furthermore, LPC upregulated the protein levels of TLR4 and p-NF-κB, activating the TLR4/NF-κB signaling pathway. Overall, our study demonstrated that LPC offsets the protective effects of BMSCs on inflammatory response and oxidative stress injury of HRMECs via TLR4/NF-κB signaling.
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Lin KT, Wang A, Nguyen AB, Iyer J, Tran SD. Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives. Biomedicines 2021; 9:1203. [PMID: 34572389 PMCID: PMC8471559 DOI: 10.3390/biomedicines9091203] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/06/2021] [Accepted: 09/09/2021] [Indexed: 11/17/2022] Open
Abstract
With the prevalence of eye diseases, such as cataracts, retinal degenerative diseases, and glaucoma, different treatments including lens replacement, vitrectomy, and stem cell transplantation have been developed; however, they are not without their respective shortcomings. For example, current methods to seal corneal incisions induced by cataract surgery, such as suturing and stromal hydration, are less than ideal due to the potential for surgically induced astigmatism or wound leakage. Vitrectomy performed on patients with diabetic retinopathy requires an artificial vitreous substitute, with current offerings having many shortcomings such as retinal toxicity. The use of stem cells has also been investigated in retinal degenerative diseases; however, an optimal delivery system is required for successful transplantation. The incorporation of hydrogels into ocular therapy has been a critical focus in overcoming the limitations of current treatments. Previous reviews have extensively documented the use of hydrogels in drug delivery; thus, the goal of this review is to discuss recent advances in hydrogel technology in surgical applications, including dendrimer and gelatin-based hydrogels for ocular adhesives and a variety of different polymers for vitreous substitutes, as well as recent advances in hydrogel-based retinal pigment epithelium (RPE) and retinal progenitor cell (RPC) delivery to the retina.
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Affiliation(s)
| | | | | | | | - Simon D. Tran
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC H3A 0C7, Canada; (K.T.L.); (A.W.); (A.B.N.); (J.I.)
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Szymanska M, Mahmood D, Yap TE, Cordeiro MF. Recent Advancements in the Medical Treatment of Diabetic Retinal Disease. Int J Mol Sci 2021; 22:ijms22179441. [PMID: 34502350 PMCID: PMC8430918 DOI: 10.3390/ijms22179441] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 08/24/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic retinal disease remains one of the most common complications of diabetes mellitus (DM) and a leading cause of preventable blindness. The mainstay of management involves glycemic control, intravitreal, and laser therapy. However, intravitreal therapy commonly requires frequent hospital visits and some patients fail to achieve a significant improvement in vision. Novel and long-acting therapies targeting a range of pathways are warranted, while evidence to support optimal combinations of treatments is currently insufficient. Improved understanding of the molecular pathways involved in pathogenesis is driving the development of therapeutic agents not only targeting visible microvascular disease and metabolic derangements, but also inflammation and accelerated retinal neurodegeneration. This review summarizes the current and emerging treatments of diabetic retinal diseases and provides an insight into the future of managing this important condition.
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Affiliation(s)
- Maja Szymanska
- The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK; (M.S.); (D.M.); (T.E.Y.)
| | - Daanyaal Mahmood
- The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK; (M.S.); (D.M.); (T.E.Y.)
| | - Timothy E. Yap
- The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK; (M.S.); (D.M.); (T.E.Y.)
| | - Maria F. Cordeiro
- The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK; (M.S.); (D.M.); (T.E.Y.)
- The Western Eye Hospital, Imperial College Healthcare NHS Trust (ICHNT), London NW1 5QH, UK
- Glaucoma and Retinal Neurodegeneration Group, Department of Visual Neuroscience, UCL Institute of Ophthalmology, London EC1V 9EL, UK
- Correspondence:
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32
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Li W, Jin L, Cui Y, Nie A, Xie N, Liang G. Bone marrow mesenchymal stem cells-induced exosomal microRNA-486-3p protects against diabetic retinopathy through TLR4/NF-κB axis repression. J Endocrinol Invest 2021; 44:1193-1207. [PMID: 32979189 DOI: 10.1007/s40618-020-01405-3] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 08/23/2020] [Indexed: 02/08/2023]
Abstract
AIM Diabetic retinopathy (DR) is a chronic disease causing health and economic burdens on individuals and society. Thus, this study is conducted to figure out the mechanisms of bone marrow mesenchymal stem cells (BMSCs)-induced exosomal microRNA-486-3p (miR-486-3p) in DR. METHODS The putative miR-486-3p binding sites to 3'untranslated region of Toll-like receptor 4 (TLR4) was verified by luciferase reporter assay. High glucose (HG)-treated Muller cells were transfected with miR-486-3p or TLR4-related oligonucleotides and plasmids to explore theirs functions in DR. Additionally, HG-treated Muller cells were co-cultured with BMSC-derived exosomes, exosomes collected from BMSCs that had been transfected with miR-486-3p or TLR4-related oligonucleotides and plasmids to explore their functions in DR. MiR-486-3p, TLR4 and nuclear factor-kappaB (NF-κB) expression, angiogenesis-related factors, oxidative stress factors, viability and apoptosis in HG-treated Muller cells were detected by RT-qPCR, western blot analysis, ELISA, MTT assay and flow cytometry, respectively. RESULTS MiR-486-3p was poorly expressed while TLR4 and NF-κB were highly expressed in HG-treated Muller cells. TLR4 was a target of miR-486-3p. Upregulating miR-486-3p or down-regulating TLR4 inhibited oxidative stress, inflammation and apoptosis, and promoted proliferation of HG-treated Muller cells. Meanwhile, BMSC-derived exosomes inhibited oxidative stress, inflammation and apoptosis, and promoted proliferation of HG-treated Muller cells. Restoring miR-486-3p further enhanced, while up-regulating TLR4 reversed, the improvement of exosomes treatment. CONCLUSION Our study highlights that up-regulation of miR-486-3p induced by BMSC-derived exosomes played a protective role in DR mice via TLR4/NF-κB axis repression.
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Affiliation(s)
- W Li
- Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China
| | - L Jin
- Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China
| | - Y Cui
- Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China
| | - A Nie
- Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China
| | - N Xie
- Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China.
| | - G Liang
- Department of Ophthalmology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 53300, Guangxi, China.
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Hu XM, Zhang Q, Zhou RX, Wu YL, Li ZX, Zhang DY, Yang YC, Yang RH, Hu YJ, Xiong K. Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications. World J Stem Cells 2021; 13:386-415. [PMID: 34136072 PMCID: PMC8176847 DOI: 10.4252/wjsc.v13.i5.386] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/26/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery. However, transplanted stem cells show a high death percentage, creating challenges to successful transplantation and prognosis. Thus, it is necessary to investigate the mechanisms underlying stem cell death, such as apoptotic cascade activation, excessive autophagy, inflammatory response, reactive oxygen species, excitotoxicity, and ischemia/hypoxia. Targeting the molecular pathways involved may be an efficient strategy to enhance stem cell viability and maximize transplantation success. Notably, a more complex network of cell death receives more attention than one crucial pathway in determining stem cell fate, highlighting the challenges in exploring mechanisms and therapeutic targets. In this review, we focus on programmed cell death in transplanted stem cells. We also discuss some promising strategies and challenges in promoting survival for further study.
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Affiliation(s)
- Xi-Min Hu
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
| | - Qi Zhang
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
| | - Rui-Xin Zhou
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
| | - Yan-Lin Wu
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
| | - Zhi-Xin Li
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
| | - Dan-Yi Zhang
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
| | - Yi-Chao Yang
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
| | - Rong-Hua Yang
- Department of Burns, Fo Shan Hospital of Sun Yat-Sen University, Foshan 528000, Guangdong Province, China
| | - Yong-Jun Hu
- Department of Cardiovascular Medicine, Hunan People's Hospital (the First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan Province, China
| | - Kun Xiong
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China.
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Miotti G, Parodi PC, Zeppieri M. Stem cell therapy in ocular pathologies in the past 20 years. World J Stem Cells 2021; 13:366-385. [PMID: 34136071 PMCID: PMC8176844 DOI: 10.4252/wjsc.v13.i5.366] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/12/2021] [Accepted: 04/26/2021] [Indexed: 02/07/2023] Open
Abstract
Stem cell therapies are successfully used in various fields of medicine. This new approach of research is also expanding in ophthalmology. Huge investments, resources and important clinical trials have been performed in stem cell research and in potential therapies. In recent years, great strides have been made in genetic research, which permitted and enhanced the differentiation of stem cells. Moreover, the possibility of exploiting stem cells from other districts (such as adipose, dental pulp, bone marrow stem cells, etc.) for the treatment of ophthalmic diseases, renders this topic fascinating. Furthermore, great strides have been made in biomedical engineering, which have proposed new materials and three-dimensional structures useful for cell therapy of the eye. The encouraging results obtained on clinical trials conducted on animals have given a significant boost in the creation of study protocols also in humans. Results are limited to date, but clinical trials continue to evolve. Our attention is centered on the literature reported over the past 20 years, considering animal (the most represented in literature) and human clinical trials, which are limiting. The aim of our review is to present a brief overview of the main types of treatments based on stem cells in the field of ophthalmic pathologies.
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Affiliation(s)
- Giovanni Miotti
- Department of Plastic Surgery, University Hospital of Udine, Udine 33100, Italy
| | - Pier Camillo Parodi
- Department of Plastic Surgery, University Hospital of Udine, Udine 33100, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy.
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Lei LM, Lin X, Xu F, Shan SK, Guo B, Li FXZ, Zheng MH, Wang Y, Xu QS, Yuan LQ. Exosomes and Obesity-Related Insulin Resistance. Front Cell Dev Biol 2021; 9:651996. [PMID: 33816504 PMCID: PMC8012888 DOI: 10.3389/fcell.2021.651996] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 02/24/2021] [Indexed: 12/13/2022] Open
Abstract
Exosomes are extracellular vesicles, delivering signal molecules from donor cells to recipient cells. The cargo of exosomes, including proteins, DNA and RNA, can target the recipient tissues and organs, which have an important role in disease development. Insulin resistance is a kind of pathological state, which is important in the pathogeneses of type 2 diabetes mellitus (T2DM), gestational diabetes mellitus and Alzheimer's disease. Furthermore, obesity is a kind of inducement of insulin resistance. In this review, we summarized recent research advances on exosomes and insulin resistance, especially focusing on obesity-related insulin resistance. These studies suggest that exosomes have great importance in the development of insulin resistance in obesity and have great potential for use in the diagnosis and therapy of insulin resistance.
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Affiliation(s)
- Li-Min Lei
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiao Lin
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Feng Xu
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Su-Kang Shan
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Bei Guo
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Fu-Xing-Zi Li
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ming-Hui Zheng
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yi Wang
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Qiu-Shuang Xu
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ling-Qing Yuan
- National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
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Li XJ, Li CY, Bai D, Leng Y. Insights into stem cell therapy for diabetic retinopathy: a bibliometric and visual analysis. Neural Regen Res 2021; 16:172-178. [PMID: 32788473 PMCID: PMC7818871 DOI: 10.4103/1673-5374.286974] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Stem cells have been confirmed to be involved in the occurrence and development of diabetic retinopathy; however, the underlying mechanisms remain unclear. In this study, we used Citespace software to visually analyze 552 articles exploring the stem cell-based treatment of diabetic retinopathy over the past 20 years, which were included in the Web of Science Core Collection. We found the following: (1) a co-citation analysis of the references cited by all 552 articles indicated 15 clusters. In cluster #0, representing the stem cell field, some highly cited landmark studies emerged between 2009–2013. For example, endothelial progenitor cells and diabetic retinopathy gradually received the full attention of scholars, in terms of their relationship and therapeutic prospects. Some researchers also verified the potential of adipose-derived stem cells to differentiate into stable retinal perivascular cells, using a variety of animal models of retinal vascular disease. All of these achievements provided references for the subsequent stem cell research. (2) An analysis of popular keywords among the 552 articles revealed that, during the past 20 years, a relative increase in basic research articles examining stem cells and endothelial progenitor cells for the treatment of diabetic retinopathy was observed. The contents of these articles primarily involved the expression of vascular endothelial growth factor, vascular regeneration, oxidative stress, and inflammatory response. (3) A burst analysis of keywords used in the 552 articles indicated that genetic and cytological research regarding the promotion of angiogenesis was an issue of concern from 2001 to 2012, including several studies addressing the expression of various growth factor genes; from 2014 to 2020, mouse models of diabetic retinopathy were recognized as mature animal models, and the most recent research has focused on macular degeneration, macular edema, neurodegeneration, and inflammatory changes in diabetic animal models. (4) Globally, the current authoritative studies have focused on basic research towards the stem cell treatment of diabetic retinopathy. Existing clinical studies are of low quality and have insufficient evidence levels, and their findings have not yet been widely accepted in clinical practice. Major challenges during stem cell transplantation remain, including stem cell heterogeneity, cell delivery, and the effective homing of stem cells to damaged tissue. However, clinical trials examining potential stem cell-based treatments of diabetic retinopathy, including the use of pluripotent stem cells, retinal pigment epithelial cells, bone marrow mesenchymal stem cells, and endothelial progenitor cells, are currently ongoing, and high-quality clinical evidence is likely to appear in the future, to promote clinical transformation.
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Affiliation(s)
- Xiang-Jun Li
- Department of Ophthalmology, Affiliated Hospital of Beihua University, Jilin, Jilin Province, China
| | - Chun-Yan Li
- Department of Endocrinology, Affiliated Hospital of Beihua University, Jilin, Jilin Province, China
| | - Dan Bai
- Department of Ophthalmology, Affiliated Hospital of Beihua University, Jilin, Jilin Province, China
| | - Ying Leng
- Department of Ophthalmology, Affiliated Hospital of Beihua University, Jilin, Jilin Province, China
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Stem Cells in Clinical Research and Therapy. Stem Cells 2021. [DOI: 10.1007/978-981-16-1638-9_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Gasecka A, Siwik D, Gajewska M, Jaguszewski MJ, Mazurek T, Filipiak KJ, Postuła M, Eyileten C. Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes. J Clin Med 2020; 9:E2807. [PMID: 32872672 PMCID: PMC7564566 DOI: 10.3390/jcm9092807] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 08/23/2020] [Accepted: 08/28/2020] [Indexed: 12/13/2022] Open
Abstract
Diabetes mellitus (DM) is a common disease worldwide. There is a strong association between DM and neurovascular and neurodegenerative disorders. The first group mainly consists of diabetic retinopathy, diabetic neuropathy and stroke, whereas, the second group includes Alzheimer's disease, Parkinson's disease, mild cognitive impairment and dementia. The aforementioned diseases have a common pathophysiological background including insulin resistance, oxidative stress, atherosclerosis and vascular injury. The increasing prevalence of neurovascular and neurodegenerative disorders among diabetic patients has resulted in an urgent need to develop biomarkers for their prediction and/or early detection. The aim of this review is to present the potential application of the most promising biomarkers of diabetes-related neurodegenerative and neurovascular disorders, including amylin, β-amyloid, C-reactive protein (CRP), dopamine, gamma-glutamyl transferase (GGT), glycogen synthase kinase 3β, homocysteine, microRNAs (mi-RNAs), paraoxonase 1, phosphoinositide 3-kinases, tau protein and various growth factors. The most clinically promising biomarkers of neurovascular and neurodegenerative complications in DM are hsCRP, GGT, homocysteine and miRNAs. However, all biomarkers discussed in this review could become a part of the potential multi-biomarker screening panel for diabetic patients at risk of neurovascular and neurodegenerative complications.
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Affiliation(s)
- Aleksandra Gasecka
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warsaw, Poland; (D.S.); (M.G.); (T.M.); (K.J.F.)
| | - Dominika Siwik
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warsaw, Poland; (D.S.); (M.G.); (T.M.); (K.J.F.)
| | - Magdalena Gajewska
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warsaw, Poland; (D.S.); (M.G.); (T.M.); (K.J.F.)
| | | | - Tomasz Mazurek
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warsaw, Poland; (D.S.); (M.G.); (T.M.); (K.J.F.)
| | - Krzysztof J. Filipiak
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warsaw, Poland; (D.S.); (M.G.); (T.M.); (K.J.F.)
| | - Marek Postuła
- Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, 80-211 Warsaw, Poland; (M.P.); (C.E.)
| | - Ceren Eyileten
- Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, 80-211 Warsaw, Poland; (M.P.); (C.E.)
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