The eye represents a highly specialized organ, with its main function being to convert light signals into electrical impulses. Any damage or disease of the eye induces a local inflammatory reaction that could be harmful for the specialized ocular cells. Therefore, the eye developed several immunoregulatory mechanisms which protect the ocular structures against deleterious immune reactions. This protection is ensured by the production of a variety of immunosuppressive molecules, which create the immune privilege of the eye. In addition, ocular cells are potent producers of numerous growth and trophic factors which support the survival and regeneration of diseased and damaged cells. If the immune privilege of the eye is interrupted and the regulatory mechanisms are not sufficiently effective, the eye disease can progress and result in worsening of vision or even blindness. In such cases, external immunotherapeutic interventions are needed. One perspective possibility of treatment is represented by mesenchymal stromal/stem cell (MSC) therapy. MSCs, which can be administered intraocularly or locally into diseased site, are potent producers of various immunoregulatory and regenerative molecules. The main advantages of MSC therapy include the safety of the treatment, the possibility to use autologous (patient's own) cells, and observations that the therapeutic properties of MSCs can be intentionally regulated by external factors during their preparation. In this review, we provide a survey of the immunoregulatory and regenerative mechanisms in the eye and describe the therapeutic potential of MSC application for corneal damages and retinal diseases.

• Klíčová slova
• cell therapy, corneal damages, immunoregulation, mesenchymal stem cells, retinal diseases, tissue regeneration,
• MeSH
• lidé MeSH
• mezenchymální kmenové buňky * cytologie   MeSH
• nemoci retiny * terapie   MeSH
• poranění rohovky * terapie   MeSH
• transplantace mezenchymálních kmenových buněk * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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.

• Klíčová slova
• clinical trials, experimental models, mesenchymal stem cells, retinal degenerative diseases, stem cell therapy,
• MeSH
• autologní transplantace MeSH
• buněčná a tkáňová terapie metody   MeSH
• buněčná diferenciace MeSH
• buňky kostní dřeně cytologie   metabolismus   MeSH
• diabetická retinopatie genetika   metabolismus   patologie   terapie   MeSH
• glaukom genetika   metabolismus   patologie   terapie   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• makulární degenerace genetika   metabolismus   patologie   terapie   MeSH
• mezenchymální kmenové buňky cytologie   metabolismus   MeSH
• mezibuněčné signální peptidy a proteiny genetika   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• neurotrofní faktory genetika   metabolismus   MeSH
• retina metabolismus   patologie   MeSH
• retinopathia pigmentosa genetika   metabolismus   patologie   terapie   MeSH
• transplantace mezenchymálních kmenových buněk metody   MeSH
• tuková tkáň cytologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mezibuněčné signální peptidy a proteiny MeSH
• neurotrofní faktory MeSH

Mesenchymal stem cells (MSCs) represent a population of cells which have the ability to regulate reactivity of T and B lymphocytes by multiple mechanisms. The immunoregulatory activities of MSCs are strictly influenced by the cytokine environment. Here we show that two functionally distinct cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), significantly potentiate the ability of MSCs to inhibit IL-10 production by activated regulatory B cells (Bregs). However, MSCs in the presence of IL-4 or IFN-γ inhibit the IL-10 production by different mechanisms. Preincubation of MSCs with IFN-γ led to the suppression, but pretreatment with IL-4 of neither MSCs nor B cells resulted in the suppression of IL-10 production. The search for candidate regulatory molecules expressed in cytokine-treated MSCs revealed different patterns of the gene expression. Pretreatment of MSCs with IFN-γ, but not with IL-4, induced expression of indoleamine-2,3-dioxygenase, cyclooxygenase-2 and programmed cell death-ligand 1. To identify the molecule(s) responsible for the suppression of IL-10 production, we used specific inhibitors of the putative regulatory molecules. We found that indomethacine, an inhibitor of cyclooxygenase-2 (Cox-2) activity, completely abrogated the inhibition of IL-10 production in cultures containing MSCs and IFN-γ, but had no effect on the suppression in cell cultures containing MSCs and IL-4. The results show that MSCs can inhibit the response of B cells to one stimulus by different mechanisms in dependence on the cytokine environment and thus support the idea of the complexity of immunoregulatory action of MSCs.

• Klíčová slova
• Cyclooxygenase 2, Cytokine environment, Gene expression, IFN-γ, IL-10, IL-4, Immunoregulation, Mesenchymal stem cells, Regulatory B cells,
• MeSH
• aktivace lymfocytů účinky léků   imunologie   MeSH
• antigeny CD279 genetika   imunologie   metabolismus   MeSH
• buněčné mikroprostředí účinky léků   imunologie   MeSH
• cyklooxygenasa 2 genetika   imunologie   metabolismus   MeSH
• cytokiny imunologie   metabolismus   farmakologie   MeSH
• ELISA MeSH
• exprese genu účinky léků   genetika   imunologie   MeSH
• indolamin-2,3,-dioxygenasa genetika   imunologie   metabolismus   MeSH
• interferon gama farmakologie   MeSH
• interleukin-10 imunologie   metabolismus   MeSH
• interleukin-4 farmakologie   MeSH
• interleukin-6 genetika   imunologie   metabolismus   MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• mezenchymální kmenové buňky účinky léků   imunologie   metabolismus   MeSH
• myši MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulační B-lymfocyty účinky léků   imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD279 MeSH
• cyklooxygenasa 2 MeSH
• cytokiny MeSH
• IL4 protein, human MeSH Prohlížeč
• indolamin-2,3,-dioxygenasa MeSH
• interferon gama MeSH
• interleukin-10 MeSH
• interleukin-4 MeSH
• interleukin-6 MeSH
• PDCD1 protein, human MeSH Prohlížeč

The aim of this study was to investigate the effects of systemically administered bone-marrow-derived mesenchymal stromal cells (MSCs) on the early acute phase of inflammation in the alkali-burned eye. Mice with damaged eyes were either untreated or treated 24 h after the injury with an intravenous administration of fluorescent-dye-labeled MSCs that were unstimulated or pretreated with interleukin-1α (IL-1α), transforming growth factor-β (TGF-β), or interferon-γ (IFN-γ). Analysis of cell suspensions prepared from the eyes of treated mice on day 3 after the alkali burn revealed that MSCs specifically migrated to the damaged eye and that the number of labeled MSCs was more than 30-times higher in damaged eyes compared with control eyes. The study of the composition of the leukocyte populations within the damaged eyes showed that all types of tested MSCs slightly decreased the number of infiltrating lymphoid and myeloid cells, but only MSCs pretreated with IFN-γ significantly decreased the percentage of eye-infiltrating cells with a more profound effect on myeloid cells. Determining cytokine and NO production in the damaged eyes confirmed that the most effective immunomodulation was achieved with MSCs pretreated with IFN-γ, which significantly decreased the levels of the proinflammatory molecules IL-1α, IL-6, and NO. Taken together, the results show that systemically administered MSCs specifically migrate to the damaged eye and that IFN-γ-pretreated MSCs are superior in inhibiting the acute phase of inflammation, decreasing leukocyte infiltration, and attenuating the early inflammatory environment.

• MeSH
• alkálie toxicita   MeSH
• alografty MeSH
• antivirové látky farmakologie   MeSH
• chemické popálení patologie   terapie   MeSH
• interferon gama farmakologie   MeSH
• interleukin-1alfa metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nika kmenových buněk * MeSH
• popálení oka chemicky indukované   metabolismus   patologie   terapie   MeSH
• transformující růstový faktor beta metabolismus   MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• zánět chemicky indukované   metabolismus   terapie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkálie MeSH
• antivirové látky MeSH
• interferon gama MeSH
• interleukin-1alfa MeSH
• transformující růstový faktor beta MeSH

Ocular surface defects represent one of the most common causes of impaired vision or even blindness. For treatment, keratoplasty represents the first choice. However, if corneal defects are more extensive and associated with a limbal stem cell (LSC) deficiency, corneal transplantation is not a sufficient therapeutic procedure and only viable approach to treatment is the transplantation of LSCs. When the LSC deficiency is a bilateral disorder, autologous LSCs are not available. The use of allogeneic LSCs requires strong immunosuppression, which leads to side-effects, and the treatment is not always effective. The alternative and perspective approach to the treatment of severe ocular surface injuries and LSC deficiency is offered by the transplantation of autologous mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of the particular patient, grow well in vitro and can be transferred, using an appropriate scaffold, onto the damaged ocular surface. Here they exert beneficial effects by possible direct differentiation into corneal epithelial cells, by immunomodulatory effects and by the production of numerous trophic and growth factors. Recent experiments utilizing the therapeutic properties of MSCs in animal models with a mechanically or chemically injured ocular surface have yielded promising results and demonstrated significant corneal regeneration, improved corneal transparency and a rapid healing process associated with the restoration of vision. The use of autologous MSCs thus represents a promising therapeutic approach and offers hope for patients with severe ocular surface injuries and LSC deficiency.

• MeSH
• autologní transplantace MeSH
• biologické modely MeSH
• buněčná diferenciace MeSH
• buňky kostní dřeně cytologie   metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   metabolismus   MeSH
• mezibuněčné signální peptidy a proteiny metabolismus   MeSH
• nanovlákna * MeSH
• nemoci rohovky chirurgie   MeSH
• pohyb buněk MeSH
• transplantace kmenových buněk metody   MeSH
• transplantace mezenchymálních kmenových buněk metody   MeSH
• tuková tkáň cytologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CD antigeny MeSH
• mezibuněčné signální peptidy a proteiny MeSH