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Chen YJ, Chang R, Fan YJ, Yang KC, Wang PY, Tseng CL. Binary Colloidal Crystals (BCCs) Modulate the Retina-related Gene Expression of hBMSCs – A Preliminary Study. Colloids Surf B Biointerfaces 2022; 218:112717. [PMID: 35961109 DOI: 10.1016/j.colsurfb.2022.112717] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 07/18/2022] [Accepted: 07/21/2022] [Indexed: 11/26/2022]
Abstract
Surface topography-induced lineage commitment of human bone marrow stem cells (hBMSCs) has been reported. However, this effect on hBMSC differentiation toward retinal pigment epithelium (RPE)-like cells has not been explored. Herein, a family of cell culture substrates called binary colloidal crystals (BCCs) was used to stimulate hBMSCs into RPE-like cells without induction factors. Two BCCs, named SiPS (silica (Si)/polystyrene (PS)) and SiPSC (Si/carboxylated PS), having similar surface topographies but different surface chemistry was used for cell culture. The result showed that cell proliferation was no difference between the two BCCs and tissue culture polystyrene (TCPS) control. However, the cell attachment, spreading area, and aspect ratio between surfaces were significantly changed. For example, cells displayed more elongated on SiPS (aspect ratio ~7.0) than those on SiPSC and TCPS (~2.0). The size of focal adhesions on SiPSC (~1.6 µm2) was smaller than that on the TCPS (~2.5 µm2). qPCR results showed that hBMSCs expressed higher RPE progenitor genes (i.e., MITF and PAX6) on day 15, and mature RPE genes (i.e., CRALBP and RPE65) on day 30 on SiPS than TCPS. On the other hand, the expression of optical vesicle or neuroretina genes (i.e., MITF and VSX2) was upregulated on day 15 on SiPSC compared to the TCPS. This study reveals that hBMSCs could be modulated into different cell subtypes depending on the BCC combinations. This study shows the potential of BCCs in controlling stem cell differentiation.
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Bacci GM, Becherucci V, Marziali E, Sodi A, Bambi F, Caputo R. Treatment of Inherited Retinal Dystrophies with Somatic Cell Therapy Medicinal Product: A Review. Life (Basel) 2022; 12:life12050708. [PMID: 35629375 PMCID: PMC9147057 DOI: 10.3390/life12050708] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/05/2022] [Accepted: 05/06/2022] [Indexed: 01/06/2023] Open
Abstract
Inherited retinal dystrophies and retinal degenerations related to more common diseases (i.e., age-related macular dystrophy) are a major issue and one of the main causes of low vision in pediatric and elderly age groups. Advancement and understanding in molecular biology and the possibilities raised by gene-editing techniques opened a new era for clinicians and patients due to feasible possibilities of treating disabling diseases and the reduction in their complications burden. The scope of this review is to focus on the state-of-the-art in somatic cell therapy medicinal products as the basis of new insights and possibilities to use this approach to treat rare eye diseases.
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Affiliation(s)
- Giacomo Maria Bacci
- Pediatric Ophthalmology Unit, Children’s Hospital A. Meyer-University of Florence, 50139 Florence, Italy; (E.M.); (R.C.)
- Correspondence:
| | - Valentina Becherucci
- Cell Factory Meyer, Children’s Hospital A. Meyer-University of Florence, 50139 Florence, Italy; (V.B.); (F.B.)
| | - Elisa Marziali
- Pediatric Ophthalmology Unit, Children’s Hospital A. Meyer-University of Florence, 50139 Florence, Italy; (E.M.); (R.C.)
| | - Andrea Sodi
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, 50139 Florence, Italy;
| | - Franco Bambi
- Cell Factory Meyer, Children’s Hospital A. Meyer-University of Florence, 50139 Florence, Italy; (V.B.); (F.B.)
| | - Roberto Caputo
- Pediatric Ophthalmology Unit, Children’s Hospital A. Meyer-University of Florence, 50139 Florence, Italy; (E.M.); (R.C.)
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3
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Knockdown of circRNA-Memo1 Reduces Hypoxia/Reoxygenation Injury in Human Brain Endothelial Cells Through miRNA-17-5p/SOS1 Axis. Mol Neurobiol 2022; 59:2085-2097. [PMID: 35041140 DOI: 10.1007/s12035-022-02743-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 01/09/2022] [Indexed: 12/23/2022]
Abstract
Circ-Memo1 has been proved to be upregulated in ischemia-reperfusion induced acute injury of kidney tissues. However, the potential role of circ-Memo1 in cerebral hypoxia/reoxygenation (H/R) injury is still unclear.Blood samples were collected from 25 ischemic stroke patients and 25 healthy controls. To construct the H/R model, human brain microvascular endothelial cells (HBMVECs) were cultured under the hypoxic condition, followed by reoxygenation. Cell viability was analyzed by MTT assay. Flow cytometry was carried out to examine cell apoptosis. The level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured by MDA and SOD assay kits, respectively. The levels of TNF-α, IL-1β, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter gene detection was employed to verify the binding relationships between circ-Memo1, miR-17-5p, and SOS1.Circ-Memo1 and SOS1 expressions were increased, and miR-17-5p expression was reduced in ischemic stroke patients. Circ-Memo1 silencing promoted cell viability, inhibited the activation of ERK/NF-κB signaling pathway, reduced oxidative stress and inflammatory response, and inhibited cell apoptosis. Moreover, miR-17-5p functioned as the sponge of circ-Memo1, and SOS1 was identified as the target of miR-17-5p. The protective effect of circ-Memo1 knockdown on cell injury after H/R treatment was weakened by miR-17-5p inhibition.Knockdown of circ-Memo1 alleviated H/R injury of HBMVEC cells by regulating the miR-17-5p/SOS1 axis, indicating that circ-Memo1 might be a potential treatment target for cerebral H/R injury.
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Tan S, Yao Y, Yang Q, Yuan XL, Cen LP, Ng TK. Diversified Treatment Options of Adult Stem Cells for Optic Neuropathies. Cell Transplant 2022; 31. [PMID: 36165292 PMCID: PMC9523835 DOI: 10.1177/09636897221123512] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 07/28/2022] [Accepted: 08/16/2022] [Indexed: 02/05/2023] Open
Abstract
Optic neuropathies refer to a group of ocular disorders with abnormalities or dysfunction of the optic nerve, sharing a common pathophysiology of retinal ganglion cell (RGC) death and axonal loss. RGCs, as the retinal neurons in the central nervous system, show limited capacity in regeneration or recovery upon diseases or after injuries. Critically, there is still no effective clinical treatment to cure most types of optic neuropathies. Recently, stem cell therapy was proposed as a potential treatment strategy for optic neuropathies. Adult stem cells, including mesenchymal stem cells and hematopoietic stem cells, have been applied in clinical trials based on their neuroprotective properties. In this article, the applications of adult stem cells on different types of optic neuropathies and the related mechanisms will be reviewed. Research updates on the strategies to enhance the neuroprotective effects of human adult stem cells will be summarized. This review article aims to enlighten the research scientists on the diversified functions of adult stem cells and consideration of adult stem cells as a potential treatment for optic neuropathies in future clinical practices.
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Affiliation(s)
- Shaoying Tan
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China
- School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong
- Research Centre for SHARP Vision, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Yao Yao
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China
- Shantou University Medical College, Shantou, China
| | - Qichen Yang
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
| | - Xiang-Ling Yuan
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China
- Shantou University Medical College, Shantou, China
| | - Ling-Ping Cen
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China
| | - Tsz Kin Ng
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China
- Shantou University Medical College, Shantou, China
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
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5
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Shams Najafabadi H, Sadeghi M, Zibaii MI, Soheili ZS, Samiee S, Ghasemi P, Hosseini M, Gholami Pourbadie H, Ahmadieh H, Taghizadeh S, Ranaei Pirmardan E. Optogenetic control of neural differentiation in Opto-mGluR6 engineered retinal pigment epithelial cell line and mesenchymal stem cells. J Cell Biochem 2021; 122:851-869. [PMID: 33847009 DOI: 10.1002/jcb.29918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 02/26/2021] [Accepted: 03/01/2021] [Indexed: 11/11/2022]
Abstract
In retinal degenerative disorders, when neural retinal cells are damaged, cell transplantation is one of the most promising therapeutic approaches. Optogenetic technology plays an essential role in the neural differentiation of stem cells via membrane depolarization. This study explored the efficacy of blue light stimulation in neuroretinal differentiation of Opto-mGluR6-engineered mouse retinal pigment epithelium (mRPE) and bone marrow mesenchymal stem cells (BMSCs). mRPE and BMSCs were selected for optogenetic study due to their capability to differentiate into retinal-specific neurons. BMSCs were isolated and phenotypically characterized by the expression of mesenchymal stem cell-specific markers, CD44 (99%) and CD105 (98.8%). mRPE culture identity was confirmed by expression of RPE-specific marker, RPE65, and epithelial cell marker, ZO-1. mRPE cells and BMSCs were transduced with AAV-MCS-IRES-EGFP-Opto-mGluR6 viral vector and stimulated for 5 days with blue light (470 nm). RNA and protein expression of Opto-mGluR6 were verified. Optogenetic stimulation-induced elevated intracellular Ca2+ levels in mRPE- and BMS-treated cells. Significant increase in cell growth rate and G1/S phase transition were detected in mRPE- and BMSCs-treated cultures. Pou4f1, Dlx2, Eomes, Barlh2, Neurod2, Neurod6, Rorb, Rxrg, Nr2f2, Ascl1, Hes5, and Sox8 were overexpressed in treated BMSCs and Barlh2, Rorb, and Sox8 were overexpressed in treated mRPE cells. Expression of Rho, Thy1, OPN1MW, Recoverin, and CRABP, as retinal-specific neuron markers, in mRPE and BMS cell cultures were demonstrated. Differentiation of ganglion, amacrine, photoreceptor cells, and bipolar and Muller precursors were determined in BMSCs-treated culture and were compared with mRPE. mRPE cells represented more abundant terminal Muller glial differentiation compared with BMSCs. Our results also demonstrated that optical stimulation increased the intracellular Ca2+ level and proliferation and differentiation of Opto-mGluR6-engineered BMSCs. It seems that optogenetic stimulation of mRPE- and BMSCs-engineered cells would be a potential therapeutic approach for retinal degenerative disorders.
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Affiliation(s)
- Hoda Shams Najafabadi
- Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Mehdi Sadeghi
- Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Mohammad I Zibaii
- Laser & Plasma Research Institute, Shahid Beheshti University, Tehran, Iran
| | - Zahra-Soheila Soheili
- Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Shahram Samiee
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Pouria Ghasemi
- Laser & Plasma Research Institute, Shahid Beheshti University, Tehran, Iran
| | - Mohammad Hosseini
- Laser & Plasma Research Institute, Shahid Beheshti University, Tehran, Iran
| | | | - Hamid Ahmadieh
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepideh Taghizadeh
- Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Ehsan Ranaei Pirmardan
- Molecular Biomarkers Nano-imaging Laboratory, Brigham & Women's Hospital, Department of Radiology, Harvard Medical School, Boston, MA, USA
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6
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Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials. Cells 2021; 10:cells10030588. [PMID: 33799995 PMCID: PMC8001847 DOI: 10.3390/cells10030588] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 02/26/2021] [Accepted: 03/02/2021] [Indexed: 12/13/2022] Open
Abstract
Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.
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7
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Li B, Jiang H, Li H, Zhang B, Slaughter M, Yan Z, Feng J. Direct conversion of adult human retinal pigmented epithelium cells to neurons with photoreceptor properties. Exp Biol Med (Maywood) 2020; 246:240-248. [PMID: 33070653 DOI: 10.1177/1535370220963755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Degeneration of photoreceptors is a major cause of blindness. Identifying new methods for the generation of photoreceptors offers valuable options for a cell replacement therapy of blindness. Here, we show that primary adult human retinal pigmented epithelium (hRPE) cells were directly converted to postmitotic neurons with various properties of photoreceptors by the neurogenic transcription factor ASCL1 and microRNA124. At Day 8 after the induction of ASCL1 and miRNA124 expression in hRPE cells, 91% of all cells were Tuj1+, and 83% of all cells were MAP2+ neurons. The cone photoreceptor marker L/M-opsin, the rod photoreceptor marker rhodopsin, and the generic photoreceptor marker recoverin were expressed in 76%, 86%, and 92% of all cells, respectively. Real-time quantitative PCR measurements showed significant and continuous increases in the expression of photoreceptor markers phosducin and recoverin, rod cell markers phosphodiesterases 6 b and arrestin S-antigen, and cone cell markers L/M-opsin and S-opsin in three independent lines of primary hRPE cells at different days of transdifferentiation. Transmission electron microscopy of converted neurons showed disc-like structures similar to those found in photoreceptors. While the converted neurons had voltage-dependent Na+, K+, and Ca2+ currents, light-induced change in membrane potential was not detected. The study demonstrates the feasibility of rapid and efficient transdifferentiation of adult hPRE cells to neurons with many properties of photoreceptors. It opens up a new possibility in cell replacement therapy of blindness caused by photoreceptor degeneration.
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Affiliation(s)
- Bo Li
- Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14203, USA
| | - Houbo Jiang
- Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14203, USA
| | - Hong Li
- Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14203, USA
| | - Boyang Zhang
- Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14203, USA
| | - Malcolm Slaughter
- Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14203, USA
| | - Zhen Yan
- Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14203, USA
| | - Jian Feng
- Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14203, USA
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Won Lee G, Thangavelu M, Joung Choi M, Yeong Shin E, Sol Kim H, Seon Baek J, Woon Jeong Y, Eun Song J, Carlomagno C, Miguel Oliveira J, Luis Reis R, Khang G. Exosome mediated transfer of miRNA‐140 promotes enhanced chondrogenic differentiation of bone marrow stem cells for enhanced cartilage repair and regeneration. J Cell Biochem 2020; 121:3642-3652. [DOI: 10.1002/jcb.29657] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 08/13/2019] [Indexed: 12/21/2022]
Affiliation(s)
- Gi Won Lee
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
| | - Muthukumar Thangavelu
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
| | - Min Joung Choi
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
| | - Eun Yeong Shin
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
| | - Han Sol Kim
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
| | - Jong Seon Baek
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
| | - Young Woon Jeong
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
| | - Jeong Eun Song
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
| | - Cristiano Carlomagno
- Department of Industrial EngineeringUniversity of TrentoTrento Italy
- BIOTech Research CenterUniversity of TrentoTrento Italy
- European Institute of Excellence on Tissue Engineering and Regenerative MedicineTrento Italy
| | - Joaquim Miguel Oliveira
- 3B's Research Group—Biomaterials, Biodegradables and BiomimeticsUniversity of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineGuimarães Portugal
| | - Rui Luis Reis
- 3B's Research Group—Biomaterials, Biodegradables and BiomimeticsUniversity of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineGuimarães Portugal
| | - Gilson Khang
- Department of BIN Convergence Technology, Department of Polymer Nano Science and Technology and Polymer Materials Fusion Research CenterChonbuk National UniversityDeokjin‐gu Jeonju Republic of Korea
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9
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Overexpression of MiR-183/96/182 Triggers Retina-Like Fate in Human Bone Marrow-Derived Mesenchymal Stem Cells (hBMSCs) in Culture. J Ophthalmol 2019; 2019:2454362. [PMID: 31885884 PMCID: PMC6927023 DOI: 10.1155/2019/2454362] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 05/30/2019] [Accepted: 07/30/2019] [Indexed: 12/12/2022] Open
Abstract
Retinal degeneration is considered as a condition ensued by different blinding disorders such as retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy, which can cause loss of photoreceptor cells and also lead to significant vision deficiencies. Although there is no efficient treatment in this domain, transplantation of stem cells has been regarded as a therapeutic approach for retinal degeneration. Thus, the purpose of this study was to analyze the potential of human bone marrow-derived mesenchymal stem cells (hBMSCs) to differentiate into photoreceptor cells via transfection of microRNA (miRNA) in vitro for regenerative medicine purposes. To this end, miR-183/96/182 cluster was transfected into hBMSCs; then, qRT-PCR was performed to measure the expression levels of miR-183/96/182 cluster and some retina-specific neuronal genes such as OTX2, NRL, PKCα, and recoverin. CRX and rhodopsin (RHO) levels were also measured through qRT-PCR and immunocytochemistry, and subsequently, cellular change morphology was detected. The findings showed no changes in the morphology of the given cells, and the expression of the neuroretinal genes such as OTX2, NRL, and PKCα. Moreover, recoverin was upregulated upon miR-183/-96/-182 overexpression in cultured hBMSCs. Ectopic overexpression of the miR-183 cluster could further increase the expression of CRX and RHO at the messenger RNA (mRNA) and protein levels. Furthermore, the data indicated that the miR-183 cluster could serve as a crucial function in photoreceptor cell differentiation. In fact, miRNAs could be assumed as potential targets to exploit silent neuronal differentiation. Ultimately, it was suggested that in vitro overexpression of miR-183 cluster could trigger reprogramming of the hBMSCs to retinal neuron fate, especially photoreceptor cells.
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Holan V, Hermankova B, Krulova M, Zajicova A. Cytokine interplay among the diseased retina, inflammatory cells and mesenchymal stem cells - a clue to stem cell-based therapy. World J Stem Cells 2019; 11:957-967. [PMID: 31768222 PMCID: PMC6851013 DOI: 10.4252/wjsc.v11.i11.957] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 09/02/2019] [Accepted: 09/14/2019] [Indexed: 02/06/2023] Open
Abstract
Retinal degenerative disorders, such as diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration or glaucoma, represent the most common causes of loss of vision and blindness. In spite of intensive research, treatment options to prevent, stop or cure these diseases are limited. Newer therapeutic approaches are offered by stem cell-based therapy. To date, various types of stem cells have been evaluated in a range of models. Among them, mesenchymal stem/stromal cells (MSCs) derived from bone marrow or adipose tissue and used as autologous cells have been proposed to have the potential to attenuate the negative manifestations of retinal diseases. MSCs delivered to the vicinity of the diseased retina can exert local anti-inflammatory and repair-promoting/regenerative effects on retinal cells. However, MSCs also produce numerous factors that could have negative impacts on retinal regeneration. The secretory activity of MSCs is strongly influenced by the cytokine environment. Therefore, the interactions among the molecules produced by the diseased retina, cytokines secreted by inflammatory cells and factors produced by MSCs will decide the development and propagation of retinal diseases. Here we discuss the interactions among cytokines and other factors in the environment of the diseased retina treated by MSCs, and we present results supporting immunoregulatory and trophic roles of molecules secreted in the vicinity of the retina during MSC-based therapy.
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Affiliation(s)
- Vladimir Holan
- Department of Transplantation Immunology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 14220, Czech Republic
- Department of Cell Biology, Faculty of Science, Charles University, Prague 12843, Czech Republic
| | - Barbora Hermankova
- Department of Transplantation Immunology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 14220, Czech Republic
- Department of Cell Biology, Faculty of Science, Charles University, Prague 12843, Czech Republic
| | - Magdalena Krulova
- Department of Transplantation Immunology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 14220, Czech Republic
- Department of Cell Biology, Faculty of Science, Charles University, Prague 12843, Czech Republic
| | - Alena Zajicova
- Department of Transplantation Immunology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 14220, Czech Republic
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11
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Adipose-derived stem cells undergo differentiation after co-culture with porcine limbal epithelial stem cells. Stem Cell Res 2019; 41:101609. [PMID: 31706096 DOI: 10.1016/j.scr.2019.101609] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 09/12/2019] [Accepted: 10/02/2019] [Indexed: 12/14/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are objects of interest in regenerative medicine. They are used for various therapies such as for the regeneration of bone, chondrocytes and other tissues. Adipose derived stem cells (ADSCs) inter alia are particularly easy to access, they are relatively abundant in fat tissue. ADSCs could be differentiated into many types of cells. To date, it has been proven that ADSCs only differentiate into mesodermal cell lineages. In this study, we present the differentiation of ADSCs into the corneal epithelium. Human ADSCs were placed in a co-culture with porcine limbal epithelial stem cells (LESCs). After 14 days of cultivation, total RNA was extracted for the analysis of the molecular markers (expression of genes of interest). The gene expression was assessed by real-time RT-qPCR. The expression of the surface molecular markers of ADSCs is modulated after co-culturing. We have observed the decrease in CD73, CD90 and CD105 mRNA expression, while the expression of mRNA coding for CK3 and CK12 mRNA was increased in ADSCs co-cultured with porcine limbal epithelial stem cells as compared to the control. We conclude that the co-culture of LESCs and ADSCs changed ADSCs' molecular markers gene expression indicating initiation of differentiation towards limbal cells.
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12
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Xie P, Deng M, Sun QG, Ma YG, Zhou Y, Ming JH, Chen Q, Liu SQ, Liu JQ, Cai J, Wu F. Therapeutic effect of transplantation of human bone marrow‑derived mesenchymal stem cells on neuron regeneration in a rat model of middle cerebral artery occlusion. Mol Med Rep 2019; 20:3065-3074. [PMID: 31432152 PMCID: PMC6755237 DOI: 10.3892/mmr.2019.10536] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 05/31/2019] [Indexed: 12/15/2022] Open
Abstract
Human bone marrow-derived mesenchymal stromal cells (hBMSCs) have been revealed to be beneficial for the regeneration of tissues and cells in several diseases. The present study aimed to elucidate the mechanisms underlying the effect of hBMSC transplantation on neuron regeneration in a rat model of middle cerebral artery occlusion (MCAO). The hBMSCs were isolated, cultured and identified. A rat model of MCAO was induced via the modified Longa method. Neurological severity scores (NSS) were adopted for the evaluation of neuronal function in the model rats after cell transplantation. Next, the expression levels of nestin, β-III-tubulin (β-III-Tub), glial fibrillary acidic protein (GFAP), HNA and neuronal nuclear antigen (NeuN) were examined, as well as the positive expression rates of human neutrophil alloantigen (HNA), nestin, NeuN, β-III-Tub and GFAP. The NSS, as well as the mRNA and protein expression of nestin, decreased at the 1st, 2nd, 4 and 8th weeks, while the mRNA and protein expression of NeuN, β-III-Tub and GFAP increased with time. In addition, after treatment, the MCAO rats showed decreased NSS and mRNA and protein expression of nestin, but elevated mRNA and protein expression of NeuN, β-III-Tub and GFAP at the 2nd, 4 and 8th weeks, and decreased positive expression of HNA and nestin with enhanced expression of NeuN, β-III-Tub and GFAP. Therefore, the present findings demonstrated that hBMSC transplantation triggered the formation of nerve cells and enhanced neuronal function in a rat model of MCAO.
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Affiliation(s)
- Ping Xie
- Department of Chinese Traditional Medicine, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, Hubei 430060, P.R. China
| | - Ming Deng
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Qin-Guo Sun
- Department of Chinese Traditional Medicine, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, Hubei 430060, P.R. China
| | - Yong-Gang Ma
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Yan Zhou
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Jiang-Hua Ming
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Qing Chen
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Shi-Qing Liu
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Jun-Qi Liu
- Department of Radiation Oncology, The First of Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 45003, P.R. China
| | - Jun Cai
- Department of Emergency and Trauma Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China
| | - Fei Wu
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
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Generation of Retinal Pigmented Epithelium-Like Cells from Pigmented Spheres Differentiated from Bone Marrow Stromal Cell-Derived Neurospheres. Tissue Eng Regen Med 2019; 16:253-263. [PMID: 31205854 DOI: 10.1007/s13770-019-00183-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 01/18/2019] [Accepted: 01/29/2019] [Indexed: 01/31/2023] Open
Abstract
Background Retinal degeneration causes blindness, and cell replacement is a potential therapy. The purpose of this study is to formation of pigmented neurospheres in a simple medium, low-cost, high-performance manner over a short period of time while expressing markers of RPE cells and the activation of specific genes of the pigment cells. Also, these neurospheres have the ability to produce a monolayer of retinal pigment epithelium-like cells (RPELC) with the ability of photoreceptor outer segment phagocytosis. Methods BMSC were isolated from pigmented hooded male rats and were immunoreactive to BMSC markers, then converted into neurospheres, differentiated into pigmented spheres (PS), and characterized using Retinal pigment epithelium-specific 65 kDa protein (RPE65), Retinaldehyde-binding protein 1 (CRALBP) and orthodenticle homeobox 2 (OTX2) markers by immunocytochemistry, RT-PCR and RT-qPCR. The PS were harvested into RPELC. The functionality of RPELC was evaluated by phagocytosis of fluorescein-labeled photoreceptor outer segment. Results The BMSC immunophenotype was confirmed by immunostained for fibronectin, CD90, CD166 and CD44. These cells differentiated into osteogenic and lipogenic cells. The generated neurospheres were immunoreactive to nestin and stemness genes. The PS after 7-14 days were positive for RPE65 (92.76-100%), CRALBP (95.21-100%) and OTX2 (94.88-100%), and after 30 days RT-PCR, qPCR revealed increasing in gene expression. The PS formed a single layer of RPELC after cultivation and phagocyte photoreceptor outer segments. Conclusion Bone marrow stromal stem cells can differentiate into functional retinal pigmented epithelium cells in a simple, low-cost, high-performance manner over a short period of time. These cells due to expressing the RPELC genes and markers can be used in cell replacement therapy for degenerative diseases including age-related macular degeneration as well as retinitis pigmentosa.
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14
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Holan V, Hermankova B, Kossl J. Perspectives of Stem Cell-Based Therapy for Age-Related Retinal Degenerative Diseases. Cell Transplant 2018; 26:1538-1541. [PMID: 29113466 PMCID: PMC5680954 DOI: 10.1177/0963689717721227] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell-based therapy that could replace diseased or missing retinal cells and support regeneration. In this respect, mesenchymal stem cells (MSCs) that can be obtained from the particular patient and used as autologous cells have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of pro-inflammatory cytokines by retinal tissue, and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.
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Affiliation(s)
- Vladimir Holan
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic.,2 Department of Cell Biology, Faculty of Natural Science, Charles University, Prague, Czech Republic
| | - Barbora Hermankova
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic.,2 Department of Cell Biology, Faculty of Natural Science, Charles University, Prague, Czech Republic
| | - Jan Kossl
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic.,2 Department of Cell Biology, Faculty of Natural Science, Charles University, Prague, Czech Republic
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15
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Enzmann V, Lecaudé S, Kruschinski A, Vater A. CXCL12/SDF-1-Dependent Retinal Migration of Endogenous Bone Marrow-Derived Stem Cells Improves Visual Function after Pharmacologically Induced Retinal Degeneration. Stem Cell Rev Rep 2017; 13:278-286. [PMID: 27924617 DOI: 10.1007/s12015-016-9706-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Mobilized bone marrow-derived stem cells (BMSC) have been discussed as an alternative strategy for endogenous repair. Thereby, different approaches for BMSC mobilization have been pursued. Herein, the role of a newly discovered oligonucleotide for retinal homing and regeneration capability of BMSCs was investigated in the sodium iodate (NaIO3) model of retinal degeneration. Mobilization was achieved in GFP-chimera with NOX-A12, a CXC-motif chemokine ligand 12 (CXCL12)/stromal cell-derived factor 1 (SDF-1)-neutralizing L-aptamer. BMSC homing was directed by intravitreal SDF-1 injection. Visual acuity was measured using the optokinetic reflex. Paraffin cross sections were stained with hematoxylin and eosin for retinal thickness measurements. Immunohistochemistry was performed to investigate the expression of cell-specific markers after mobilization. A single dose of NOX-A12 induced significant mobilization of GFP+ cells which were found in all layers within the degenerating retina. An additional intravitreal injection of SDF-1 increased migration towards the site of injury. Thereby, the number of BMSCs (Sca-1+) found in the damaged retina increased whereas a decrease of activated microglia (Iba-1+) was found. The mobilization led to significantly increased visual acuity. However, no significant changes in retinal thickness or differentiation towards retinal cell types were detected. Systemic mobilization by a single dose of NOX-A12 showed increased homing of BMSCs into the degenerated retina, which was associated with improved visual function when injection of SDF-1 was additionally performed. The redistribution of the cells to the site of injury combined with their observed beneficial effects support the endogenous therapeutic strategy for retinal repair.
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Affiliation(s)
- Volker Enzmann
- Department of Ophthalmology, University Hospital, University of Bern, Freiburgstrasse 14, 3010, Bern, Switzerland. .,Department of Clinical Research, University of Bern, Bern, Switzerland.
| | - Stéphanie Lecaudé
- Department of Clinical Research, University of Bern, Bern, Switzerland
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16
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Lu W, Duan D, Ackbarkhan Z, Lu M, Huang ML. Differentiation of human olfactory mucosa mesenchymal stem cells into photoreceptor cells in vitro. Int J Ophthalmol 2017; 10:1504-1509. [PMID: 29062767 DOI: 10.18240/ijo.2017.10.04] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 08/01/2017] [Indexed: 11/23/2022] Open
Abstract
AIM To investigate whether the human olfactory mucosa mesenchymal stem cells (OM-MSCs) can differentiate into photoreceptor cells in vitro. METHODS Through the olfactory mucosa adherent method, olfactory mucosa was isolated, cultured and identified in vitro among mesenchymal stem cells. The cell surface markers were analyzed by flow cytometry, induced to differentiate into retinal photoreceptor cells in vitro, and the expression of rhodopsin was observed and identified by Immunofluorescence and Western blot methods. RESULTS OM-MSCs from human were spindle cell-based, and showing radial colony arrangement. OM-MSCs were negative for CD34, CD45 and CD105, but positive for CD73 and CD90. Following induction, a strong positive reaction was produced by photoreceptor specific marker rhodopsin in the cells. CONSLUSION This novel finding demonstrates that OM-MSCs can be cultured and expanded in vitro. They possess biological characteristics of mesenchymal stem cells, and have the ability to be induced into retinal cells.
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Affiliation(s)
- Wen Lu
- Department of Ophthalmology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Da Duan
- Department of Neurosurgery, the 163rd Hospital of Chinese PLA, the Second Affiliated Hospital of Hunan Normal University, Changsha 410003, Hunan Province, China
| | - Zacharia Ackbarkhan
- Department of Ophthalmology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ming Lu
- Department of Neurosurgery, the 163rd Hospital of Chinese PLA, the Second Affiliated Hospital of Hunan Normal University, Changsha 410003, Hunan Province, China
| | - Min-Li Huang
- Department of Ophthalmology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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17
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Hermankova B, Kossl J, Javorkova E, Bohacova P, Hajkova M, Zajicova A, Krulova M, Holan V. The Identification of Interferon-γ as a Key Supportive Factor for Retinal Differentiation of Murine Mesenchymal Stem Cells. Stem Cells Dev 2017; 26:1399-1408. [PMID: 28728472 DOI: 10.1089/scd.2017.0111] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Retinal disorders represent the main cause of decreased quality of vision and even blindness worldwide. The loss of retinal cells causes irreversible damage of the retina, and there are currently no effective treatment protocols for most retinal degenerative diseases. A promising approach for the treatment of retinal disorders is represented by stem cell-based therapy. The perspective candidates are mesenchymal stem cells (MSCs), which can differentiate into multiple cell types and produce a number of trophic and growth factors. In this study, we show the potential of murine bone marrow-derived MSCs to differentiate into cells expressing retinal markers and we identify the key supportive role of interferon-γ (IFN-γ) in the differentiation process. MSCs were cultured for 7 days with retinal extract and supernatant from T-cell mitogen concanavalin A-stimulated splenocytes, simulating the inflammatory site of retinal damage. MSCs cultured in such conditions differentiated to the cells expressing retinal cell markers such as rhodopsin, S antigen, retinaldehyde-binding protein, calbindin 2, recoverin, and retinal pigment epithelium 65. To identify a supportive molecule in the supernatants from activated spleen cells, MSCs were cultured with retinal extract in the presence of various T-cell cytokines. The expression of retinal markers was enhanced only in the presence of IFN-γ, and the supportive role of spleen cell supernatants was abrogated with the neutralization antibody anti-IFN-γ. In addition, differentiated MSCs were able to express a number of neurotrophic factors, which are important for retinal regeneration. Taken together, the results show that MSCs can differentiate into cells expressing retinal markers and that this differentiation process is supported by IFN-γ.
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Affiliation(s)
- Barbora Hermankova
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine , Czech Academy of Sciences, Prague, Czech Republic .,2 Department of Cell Biology, Faculty of Science, Charles University , Prague, Czech Republic
| | - Jan Kossl
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine , Czech Academy of Sciences, Prague, Czech Republic .,2 Department of Cell Biology, Faculty of Science, Charles University , Prague, Czech Republic
| | - Eliska Javorkova
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine , Czech Academy of Sciences, Prague, Czech Republic .,2 Department of Cell Biology, Faculty of Science, Charles University , Prague, Czech Republic
| | - Pavla Bohacova
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine , Czech Academy of Sciences, Prague, Czech Republic .,2 Department of Cell Biology, Faculty of Science, Charles University , Prague, Czech Republic
| | - Michaela Hajkova
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine , Czech Academy of Sciences, Prague, Czech Republic .,2 Department of Cell Biology, Faculty of Science, Charles University , Prague, Czech Republic
| | - Alena Zajicova
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine , Czech Academy of Sciences, Prague, Czech Republic
| | - Magdalena Krulova
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine , Czech Academy of Sciences, Prague, Czech Republic .,2 Department of Cell Biology, Faculty of Science, Charles University , Prague, Czech Republic
| | - Vladimir Holan
- 1 Department of Transplantation Immunology, Institute of Experimental Medicine , Czech Academy of Sciences, Prague, Czech Republic .,2 Department of Cell Biology, Faculty of Science, Charles University , Prague, Czech Republic
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Overview of retinal differentiation potential of mesenchymal stem cells: A promising approach for retinal cell therapy. Ann Anat 2016; 210:52-63. [PMID: 27986614 DOI: 10.1016/j.aanat.2016.11.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Revised: 10/10/2016] [Accepted: 11/11/2016] [Indexed: 12/15/2022]
Abstract
Retinal disease caused by retinal cell apoptosis leads to irreversible vision loss. Stem cell investigation efforts have been made to solve and cure retinal disorders. There are several sources of stem cells which have been used in these experiments. Numerous studies demonstrated that transplanted stem cells can migrate into and integrate in different layers of retina. Among these, mesenchymal stem cells (MSCs) were considered a promising source for cell therapy. Here, we review the literature assessing the potential of MSCs to differentiate into retinal cells in vivo and in vitro as well as their clinical application. However, more investigation is required to define the protocols that optimize stem cell differentiation and their functional integration in the retina.
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19
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Fronk AH, Vargis E. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations. J Tissue Eng 2016; 7:2041731416650838. [PMID: 27493715 PMCID: PMC4959307 DOI: 10.1177/2041731416650838] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 04/23/2016] [Indexed: 12/17/2022] Open
Abstract
The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included.
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Affiliation(s)
- Aaron H Fronk
- Department of Biological Engineering, Utah State University, Logan, UT, USA
| | - Elizabeth Vargis
- Department of Biological Engineering, Utah State University, Logan, UT, USA
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Delplace V, Payne S, Shoichet M. Delivery strategies for treatment of age-related ocular diseases: From a biological understanding to biomaterial solutions. J Control Release 2015; 219:652-668. [PMID: 26435454 DOI: 10.1016/j.jconrel.2015.09.065] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 09/28/2015] [Accepted: 09/29/2015] [Indexed: 12/24/2022]
Abstract
Age-related ocular diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, result in life-long functional deficits and enormous global health care costs. As the worldwide population ages, vision loss has become a major concern for both economic and human health reasons. Due to recent research into biomaterials and nanotechnology major advances have been gained in the field of ocular delivery. This review provides a summary and discussion of the most recent strategies employed for the delivery of both drugs and cells to the eye to treat a variety of age-related diseases. It emphasizes the current challenges and limitations to ocular delivery and how the use of innovative materials can overcome these issues and ultimately provide treatment for age-related degeneration and regeneration of lost tissues. This review also provides critical considerations and an outlook for future studies in the field of ophthalmic delivery.
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Affiliation(s)
- Vianney Delplace
- Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 164 College Street, Toronto, ON M5S 3G9, Canada
| | - Samantha Payne
- Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 164 College Street, Toronto, ON M5S 3G9, Canada
| | - Molly Shoichet
- Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 164 College Street, Toronto, ON M5S 3G9, Canada.
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