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.

• Keywords
• clinical trials, experimental models, mesenchymal stem cells, retinal degenerative diseases, stem cell therapy,
• MeSH
• Transplantation, Autologous MeSH
• Cell- and Tissue-Based Therapy methods   MeSH
• Cell Differentiation MeSH
• Bone Marrow Cells cytology   metabolism   MeSH
• Diabetic Retinopathy genetics   metabolism   pathology   therapy   MeSH
• Glaucoma genetics   metabolism   pathology   therapy   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Macular Degeneration genetics   metabolism   pathology   therapy   MeSH
• Mesenchymal Stem Cells cytology   metabolism   MeSH
• Intercellular Signaling Peptides and Proteins genetics   metabolism   MeSH
• Disease Models, Animal MeSH
• Nerve Growth Factors genetics   metabolism   MeSH
• Retina metabolism   pathology   MeSH
• Retinitis Pigmentosa genetics   metabolism   pathology   therapy   MeSH
• Mesenchymal Stem Cell Transplantation methods   MeSH
• Adipose Tissue cytology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Intercellular Signaling Peptides and Proteins MeSH
• Nerve Growth Factors MeSH

Corneal alkali burns are potentially blinding injuries. Alkali induces oxidative stress in corneas followed by excessive corneal inflammation, neovascularization, and untransparent scar formation. Molecular hydrogen (H2), a potent reactive oxygen species (ROS) scavenger, suppresses oxidative stress and enables corneal healing when applied on the corneal surface. The purpose of this study was to examine whether the H2 pretreatment of healthy corneas evokes a protective effect against corneal alkali-induced oxidative stress. Rabbit eyes were pretreated with a H2 solution or buffer solution, by drops onto the ocular surface, and the corneas were then burned with 0.25 M NaOH. The results obtained with immunohistochemistry and pachymetry showed that in the corneas of H2-pretreated eyes, slight oxidative stress appeared followed by an increased expression of antioxidant enzymes. When these corneas were postburned with alkali, the alkali-induced oxidative stress was suppressed. This was in contrast to postburned buffer-pretreated corneas, where the oxidative stress was strong. These corneas healed with scar formation and neovascularization, whereas corneas of H2-pretreated eyes healed with restoration of transparency in the majority of cases. Corneal neovascularization was strongly suppressed. Our results suggest that the corneal alkali-induced oxidative stress was reduced via the increased antioxidant capacity of corneal cells against reactive oxygen species (ROS). It is further suggested that the ability of H2 to induce the increase in antioxidant cell capacity is important for eye protection against various diseases or external influences associated with ROS production.

• MeSH
• Alkalies toxicity   MeSH
• Antioxidants metabolism   MeSH
• Burns, Chemical drug therapy   metabolism   pathology   MeSH
• Epithelial Cells drug effects   metabolism   pathology   MeSH
• Wound Healing drug effects   MeSH
• Rabbits MeSH
• Disease Models, Animal MeSH
• Corneal Neovascularization prevention & control   MeSH
• Oxidative Stress drug effects   MeSH
• Eye Burns chemically induced   drug therapy   metabolism   pathology   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Cornea blood supply   drug effects   metabolism   pathology   MeSH
• Hydrogen pharmacology   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Retracted Publication MeSH
• Names of Substances
• Alkalies MeSH
• Antioxidants MeSH
• Reactive Oxygen Species MeSH
• Hydrogen MeSH

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.

• Keywords
• Cytokines, Degenerative diseases, Growth factors, Mesenchymal stem cells, Retina, Stem cell therapy,
• Publication type
• Journal Article MeSH
• Review MeSH

Immunosuppressive drugs are widely used to treat undesirable immune reaction, however their clinical use is often limited by harmful side effects. The combined application of immunosuppressive agents with mesenchymal stem cells (MSCs) offers a promising alternative approach that enables the reduction of immunosuppressive agent doses and simultaneously maintains or improves the outcome of therapy. The present study aimed to determinate the effects of immunosuppressants on individual T cell subpopulations and to investigate the efficacy of MSC-based treatment combined with immunosuppressive drugs. We tested the effect of five widely used immunosuppressants with different action mechanisms: cyclosporine A, mycophenolate mofetil, rapamycin, and two glucocorticoids - prednisone and dexamethasone in combination with MSCs on mouse CD4+ and CD8+ lymphocyte viability and activation, Th17 (RORγt+), Th1 (T-bet+), Th2 (GATA-3+) and Treg (Foxp3+) cell proportion and on the production of corresponding key cytokines (IL-17, IFNγ, IL-4 and IL-10). We showed that MSCs modulate the actions of immunosuppressants and in combination with immunosuppressive drugs display distinct effect on cell activation and balance among different T lymphocytes subpopulations and exert a suppressive effect on proinflammatory T cell subsets while promoting the functions of anti-inflammatory Treg lymphocytes. The results indicated that MSC-based therapy could be a powerful strategy to attenuate the negative effects of immunosuppressive drugs on the immune system.

• Keywords
• Immunomodulation, Immunosuppressive drugs, Mesenchymal stem cells, Stem cell therapy, T cells,
• MeSH
• Lymphocyte Activation drug effects   immunology   MeSH
• Cyclosporine pharmacology   MeSH
• Cytokines metabolism   MeSH
• Dexamethasone pharmacology   MeSH
• Glucocorticoids pharmacology   MeSH
• Immunosuppressive Agents pharmacology   MeSH
• Coculture Techniques MeSH
• Cells, Cultured MeSH
• Mycophenolic Acid pharmacology   MeSH
• Mesenchymal Stem Cells cytology   immunology   metabolism   MeSH
• Mice, Inbred BALB C MeSH
• Prednisone pharmacology   MeSH
• Cell Proliferation drug effects   MeSH
• Flow Cytometry MeSH
• Sirolimus pharmacology   MeSH
• T-Lymphocyte Subsets cytology   drug effects   immunology   MeSH
• Mesenchymal Stem Cell Transplantation methods   MeSH
• Cell Survival drug effects   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cyclosporine MeSH
• Cytokines MeSH
• Dexamethasone MeSH
• Glucocorticoids MeSH
• Immunosuppressive Agents MeSH
• Mycophenolic Acid MeSH
• Prednisone MeSH
• Sirolimus MeSH

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

• MeSH
• Alkalies MeSH
• Antioxidants therapeutic use   MeSH
• Cell Differentiation drug effects   MeSH
• Burns, Chemical enzymology   genetics   pathology   therapy   MeSH
• Immunohistochemistry MeSH
• Rabbits MeSH
• Limbus Corneae cytology   MeSH
• Matrix Metalloproteinase 9 metabolism   MeSH
• Mesenchymal Stem Cells cytology   drug effects   MeSH
• Protective Agents pharmacology   therapeutic use   MeSH
• Corneal Pachymetry MeSH
• Gene Expression Regulation drug effects   MeSH
• Epithelium, Corneal pathology   MeSH
• Superoxide Dismutase metabolism   MeSH
• Nitric Oxide Synthase Type II metabolism   MeSH
• Transforming Growth Factor beta genetics   metabolism   MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Adipocytes cytology   drug effects   MeSH
• Vascular Endothelial Growth Factor A metabolism   MeSH
• Corneal Opacity complications   therapy   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Retracted Publication MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Alkalies MeSH
• Antioxidants MeSH
• Matrix Metalloproteinase 9 MeSH
• Protective Agents MeSH
• Superoxide Dismutase MeSH
• Nitric Oxide Synthase Type II MeSH
• Transforming Growth Factor beta MeSH
• Vascular Endothelial Growth Factor A MeSH

UNLABELLED: Stem cell-based therapy has become an attractive and promising approach for the treatment of severe injuries or thus-far incurable diseases. However, the use of stem cells is often limited by a shortage of available tissue-specific stem cells; therefore, other sources of stem cells are being investigated and tested. In this respect, mesenchymal stromal/stem cells (MSCs) have proven to be a promising stem cell type. In the present study, we prepared MSCs from bone marrow (BM-MSCs) or adipose tissue (Ad-MSCs) as well as limbal epithelial stem cells (LSCs), and their growth, differentiation, and secretory properties were compared. The cells were grown on nanofiber scaffolds and transferred onto the alkali-injured eye in a rabbit model, and their therapeutic potential was characterized. We found that BM-MSCs and tissue-specific LSCs had similar therapeutic effects. Clinical characterization of the healing process, as well as the evaluation of corneal thickness, re-epithelialization, neovascularization, and the suppression of a local inflammatory reaction, were comparable in the BM-MSC- and LSC-treated eyes, but results were significantly better than in injured, untreated eyes or in eyes treated with a nanofiber scaffold alone or with a nanofiber scaffold seeded with Ad-MSCs. Taken together, the results show that BM-MSCs' therapeutic effect on healing of injured corneal surface is comparable to that of tissue-specific LSCs. We suggest that BM-MSCs can be used for ocular surface regeneration in cases when autologous LSCs are absent or difficult to obtain. SIGNIFICANCE: Damage of ocular surface represents one of the most common causes of impaired vision or even blindness. Cell therapy, based on transplantation of stem cells, is an optimal treatment. However, if limbal stem cells (LSCs) are not available, other sources of stem cells are tested. Mesenchymal stem cells (MSCs) are a convenient type of cell for stem cell therapy. The therapeutic potential of LSCs and MSCs was compared in an experimental model of corneal injury, and healing was observed following chemical injury. MSCs and tissue-specific LSCs had similar therapeutic effects. The results suggest that bone marrow-derived MSCs can be used for ocular surface regeneration in cases when autologous LSCs are absent or difficult to obtain.

• Keywords
• Alkali-injured ocular surface, Corneal regeneration, Limbal stem cells, Mesenchymal stem cells, Stem cell-based therapy,
• MeSH
• Biomarkers metabolism   MeSH
• Cell- and Tissue-Based Therapy methods   MeSH
• Cell Differentiation MeSH
• Bone Marrow Cells cytology   physiology   MeSH
• Burns, Chemical pathology   therapy   MeSH
• Epithelial Cells cytology   physiology   transplantation   MeSH
• Gene Expression MeSH
• Neovascularization, Physiologic MeSH
• Rabbits MeSH
• Limbus Corneae blood supply   injuries   MeSH
• Mesenchymal Stem Cells cytology   physiology   MeSH
• Primary Cell Culture MeSH
• Cell Proliferation MeSH
• Re-Epithelialization physiology   MeSH
• Epithelium, Corneal blood supply   injuries   MeSH
• Tissue Scaffolds MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Adipose Tissue cytology   physiology   MeSH
• Adipocytes cytology   physiology   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Biomarkers MeSH

Oxidative stress is involved in many ocular diseases and injuries. The imbalance between oxidants and antioxidants in favour of oxidants (oxidative stress) leads to the damage and may be highly involved in ocular aging processes. The anterior eye segment and mainly the cornea are directly exposed to noxae of external environment, such as air pollution, radiation, cigarette smoke, vapors or gases from household cleaning products, chemical burns from splashes of industrial chemicals, and danger from potential oxidative damage evoked by them. Oxidative stress may initiate or develop ocular injury resulting in decreased visual acuity or even vision loss. The role of oxidative stress in the pathogenesis of ocular diseases with particular attention to oxidative stress in the cornea and changes in corneal optical properties are discussed. Advances in the treatment of corneal oxidative injuries or diseases are shown.

• MeSH
• Alkalies toxicity   MeSH
• Ophthalmic Solutions therapeutic use   MeSH
• Oxidative Stress * drug effects   radiation effects   MeSH
• Corneal Injuries drug therapy   metabolism   pathology   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Cornea drug effects   radiation effects   MeSH
• Ultraviolet Rays MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Alkalies MeSH
• Ophthalmic Solutions MeSH
• Reactive Oxygen Species MeSH