Stem cell-based therapy represents a promising approach for the treatment of numerous currently uncurable diseases. However, wider application of this therapy is still bound by various limitations. To increase the effectiveness of cell therapy, a combined application of stem cells with various types of chemicals or agents, which could support the immunoregulatory and therapeutic properties of stem cells, has been proposed and tested. One prospective approach is offered by the co-application of mesenchymal stem cells (MSCs), which have potent immunomodulatory and regenerative properties, and selected metal nanoparticles (NPs) which have been used in various fields of medicine for their immunomodulatory, anti-oxidant and antibacterial properties. It has been shown that the main mechanism of the therapeutic action of MSCs is the production of immunomodulatory molecules and growth factors, and that the secretory activity of MSCs can be modified by different types of NPs. For this purpose, metal NPs are extremely useful. They possess unique characteristics and can influence the growth and repair of tissues, exert strong antimicrobial activity and serve as nanocarriers. Thus, treatment based on the simultaneous application of MSCs and selected NPs combines the therapeutic effects of MSCs and impacts of NPs on applied MSCs, and on the cells and tissues of the recipient. In this review we outline the current state of studies combining the administration of MSCs and the application of metal NPs, with a focus on perspectives to use such treatment for corneal and retinal injuries and diseases.

• Klíčová slova
• combined application, mesenchymal stem cells, metal nanoparticles, ocular disorders, therapeutic effect,
• MeSH
• kombinovaná terapie metody   MeSH
• kovové nanočástice * chemie   terapeutické užití   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * cytologie   MeSH
• oční nemoci * 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

Retinal degenerative disorders are characterized by a local upregulation of inflammatory factors, infiltration with cells of the immune system, a vascular dysfunction and by the damage of retinal cells. There is still a lack of treatment protocols for these diseases. Mesenchymal stem cell (MSC)-based therapy using immunoregulatory, regenerative and differentiating properties of MSCs offers a promising treatment option. In this study, we analyzed the immunomodulatory properties of mouse bone marrow-derived MSCs after their intravitreal delivery to the inflammatory environment in the eye, caused by the application of pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ. The intravitreal administration of these cytokines induces an increased expression of pro-inflammatory molecules such as IL-1α, IL-6, inducible nitric oxide synthase, TNF-α and vascular endothelial growth factor in the retina. However, a significant decrease in the expression of genes for all these pro-inflammatory molecules was observed after the intravitreal injection of MSCs. We further showed that an increased infiltration of the retina with immune cells, mainly with macrophages, which was observed after pro-inflammatory cytokine application, was significantly reduced after the intravitreal application of MSCs. The similar immunosuppressive effects of MSCs were also demonstrated in vitro in cultures of cytokine-stimulated retinal explants and MSCs. Overall, the results show that intravitreal application of MSCs inhibits the early retinal inflammation caused by pro-inflammatory cytokines, and propose MSCs as a promising candidate for stem cell-based therapy of retinal degenerative diseases.

• Klíčová slova
• Cytokines, Immunomodulation, Inflammation, Mesenchymal stem cells, Retina,
• MeSH
• antivirové látky farmakologie   MeSH
• cytokiny metabolismus   MeSH
• imunomodulace účinky léků   imunologie   MeSH
• interferon gama farmakologie   MeSH
• interleukin-1beta farmakologie   MeSH
• mediátory zánětu farmakologie   MeSH
• mezenchymální kmenové buňky cytologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• oxid dusnatý metabolismus   MeSH
• retina cytologie   účinky léků   imunologie   metabolismus   MeSH
• TNF-alfa farmakologie   MeSH
• zánět imunologie   metabolismus   patologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antivirové látky MeSH
• cytokiny MeSH
• IL1B protein, mouse MeSH Prohlížeč
• interferon gama MeSH
• interleukin-1beta MeSH
• mediátory zánětu MeSH
• oxid dusnatý MeSH
• TNF-alfa 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.

• Klíčová slova
• Alkali-injured ocular surface, Corneal regeneration, Limbal stem cells, Mesenchymal stem cells, Stem cell-based therapy,
• MeSH
• biologické markery metabolismus   MeSH
• buněčná a tkáňová terapie metody   MeSH
• buněčná diferenciace MeSH
• buňky kostní dřeně cytologie   fyziologie   MeSH
• chemické popálení patologie   terapie   MeSH
• epitelové buňky cytologie   fyziologie   transplantace   MeSH
• exprese genu MeSH
• fyziologická neovaskularizace MeSH
• králíci MeSH
• limbus corneae krevní zásobení   zranění   MeSH
• mezenchymální kmenové buňky cytologie   fyziologie   MeSH
• primární buněčná kultura MeSH
• proliferace buněk MeSH
• reepitalizace fyziologie   MeSH
• rohovkový epitel krevní zásobení   zranění   MeSH
• tkáňové podpůrné struktury MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• tuková tkáň cytologie   fyziologie   MeSH
• tukové buňky cytologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH