It is now widely recognized that mesenchymal stem cells (MSCs) possess the capacity to differentiate into a wide array of cell types. Numerous studies have identified the role of lncRNA in the regulation of MSC differentiation. It is important to elucidate the role and interplay of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of signalling pathways that govern MSC function. Furthermore, miRNAs and lncRNAs are important clinical for innovative strategies aimed at addressing a wide spectrum of existing and emerging disease. Hence it is important to consider their impact on MSC function and differentiation. Examining the data available in public databases, we have collected the literature containing the latest discoveries pertaining to human stem cells and their potential in both fundamental research and clinical applications. Furthermore, we have compiled completed clinical studies that revolve around the application of MSCs, shedding light on the opportunities presented by harnessing the regulatory potential of miRNAs and lncRNAs. This exploration of the therapeutic possibilities offered by miRNAs and lncRNAs within MSCs unveils exciting prospects for the development of precision therapies and personalized treatment approaches. Ultimately, these advancements promise to augment the efficacy of regenerative strategies and produce positive outcomes for patients. As research in this field continues to evolve, it is imperative to explore and exploit the vast potential of miRNAs and lncRNAs as therapeutic agents. The findings provide a solid basis for ongoing investigations, fuelling the quest to fully unlock the regenerative potential of MSCs.

• Klíčová slova
• lncRNA, mesenchymal stem cells, miRNA,
• MeSH
• buněčná diferenciace genetika   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * metabolismus   MeSH
• mikro RNA * genetika   metabolismus   MeSH
• osteoblasty metabolismus   MeSH
• RNA dlouhá nekódující * genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA * MeSH
• RNA dlouhá nekódující * MeSH

Chondropathies are increasing worldwide, but effective treatments are currently lacking. Mesenchymal stromal cell (MSCs) transplantation represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Umbilical cord- (UC-) MSCs gained increasing interest due to their multilineage differentiation potential, immunomodulatory, and anti-inflammatory properties as well as higher proliferation rates, abundant supply along with no risks for the donor compared to adult MSCs. In addition, UC-MSCs are physiologically adapted to survive in an ischemic and nutrient-poor environment as well as to produce an extracellular matrix (ECM) similar to that of the cartilage. All these characteristics make UC-MSCs a pivotal source for a stem cell-based treatment of chondropathies. In this review, the regenerative potential of UC-MSCs for the treatment of cartilage diseases will be discussed focusing on in vitro, in vivo, and clinical studies.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The primary function of the skin is that of a physical barrier against the environment and diverse pathogens; therefore, its integrity is essential for survival. Skin regeneration depends on multiple stem cell compartments within the epidermis, which, despite their different transcriptional and proliferative capacity, as well as different anatomical location, fall under the general term of skin stem cells (SSCs). Skin wounds can normally heal without problem; however, some diseases or extensive damage may delay or prevent healing. Non-healing wounds represent a serious and life-threatening scenario that may require advanced therapeutic strategies. In this regard, increased focus has been directed at SSCs and their role in wound healing, although emerging therapeutical approaches are considering the use of other stem cells instead, such as mesenchymal stem cells (MSCs). Given its extensive and broad nature, this review supplies newcomers with an introduction to SSCs, wound healing, and therapeutic strategies for skin regeneration, thus familiarizing the reader with the subject in preparation for future in depth reading.

• Klíčová slova
• non-healing wounds, skin regeneration, skin stem cells, tissue engineering, wound healing,
• MeSH
• fyziologie kůže MeSH
• hojení ran * MeSH
• kůže zranění   MeSH
• lidé MeSH
• mezenchymální kmenové buňky MeSH
• regenerace * MeSH
• tkáňové inženýrství MeSH
• transplantace mezenchymálních kmenových buněk 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) have become a promising tool in cellular therapy for restoring immune system haemostasis; however, the success of clinical trials has been impaired by the lack of standardized manufacturing processes. This study aims to determine the suitability of source tissues and culture media for the production of MSC-based advanced therapy medicinal products (ATMPs) and to define parameters to extend the set of release criteria. MSCs were isolated from umbilical cord (UC), bone marrow and lipoaspirate and expanded in three different culture media. MSC phenotype, proliferation capacity and immunosuppressive parameters were evaluated in normal MSCs compared to primed MSCs treated with cytokines mimicking an inflammatory environment. Compared to bone marrow and lipoaspirate, UC-derived MSCs (UC-MSCs) showed the highest proliferative capacity, which was further enhanced by media supplemented with bFGF, while the cells maintained their immunosuppressive characteristics. Moreover, UC-MSCs expanded in the bFGF-enriched medium were the least sensitive to undesirable priming-induced changes in the MSC phenotype. Surface markers and secreted factors were identified to reflect the cell response to inflammatory priming and to be variable among MSCs from different source tissues. This study demonstrates that UC is a favorable cell source for manufacturing MSC-based ATMPs for immunosuppressive applications. UC-MSCs are able to use the bFGF-enriched medium for higher cell yields without the impairment of immunosuppressive parameters and undesirable phenotype changes after inflammatory preconditioning of MSCs before transplantation. Additionally, immunosuppressive parameters were identified to help finding predictors of clinically efficient MSCs in the following clinical trials.

• Klíčová slova
• advanced therapy medicinal product, immunosuppression, mesenchymal stem cells, umbilical cord,
• MeSH
• buněčná diferenciace účinky léků   imunologie   MeSH
• fibroblastový růstový faktor 2 imunologie   farmakologie   MeSH
• imunosupresivní léčba * MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   imunologie   MeSH
• proliferace buněk účinky léků   MeSH
• pupečník cytologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fibroblastový růstový faktor 2 MeSH

Obesity is characterized by low-grade inflammation, which is accompanied by increased accumulation of immune cells in peripheral tissues including adipose tissue (AT), skeletal muscle, liver and pancreas, thereby impairing their primary metabolic functions in the regulation of glucose homeostasis. Obesity has also shown to have a detrimental effect on bone homeostasis by altering bone marrow and hematopoietic stem cell differentiation and thus impairing bone integrity and immune cell properties. The origin of immune cells arises in the bone marrow, which has been shown to be affected with the obesogenic condition via increased cellularity and shifting differentiation and function of hematopoietic and bone marrow mesenchymal stem cells in favor of myeloid progenitors and increased bone marrow adiposity. These obesity-induced changes in the bone marrow microenvironment lead to dramatic bone marrow remodeling and compromising immune cell functions, which in turn affect systemic inflammatory conditions and regulation of whole-body metabolism. However, there is limited information on the inflammatory secretory factors creating the bone marrow microenvironment and how these factors changed during metabolic complications. This review summarizes recent findings on inflammatory and cellular changes in the bone marrow in relation to obesity and further discuss whether dietary intervention or physical activity may have beneficial effects on the bone marrow microenvironment and whole-body metabolism.

• Klíčová slova
• bone marrow mesenchymal stem cells, bone marrow microenvironment, hematopoietic stem cells, immune responses, life-style interventions, obesity,
• MeSH
• buněčné mikroprostředí imunologie   MeSH
• hematopoetické kmenové buňky imunologie   patologie   MeSH
• hematopoéza * MeSH
• kostní dřeň imunologie   patologie   MeSH
• lidé MeSH
• obezita patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Therapeutic options for end-stage organ failure are often limited to whole organ transplantation. The tolerance or rejection of the transplanted organ is driven by both early non-specific innate and specific adaptive responses. The use of mesenchymal stromal cells (MSCs) is considered a promising tool in regenerative medicine. Human umbilical cord (HUC) is an easily available source of MSCs, without relevant ethical issues. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs), showed consistent immunomodulatory features that may be useful to promote immune tolerance in the host after transplantation. Few data are available on the phenotype of WJ-MSCs in situ. We investigated the expression of immune-related molecules, such as HLAs, IDO, CD276/B7-H3, and others, both in situ (HUC) and in in vitro-cultured WJ-MSCs. Morphological and biochemical techniques were used to define the expression of such molecules. In addition, we focused on the possible role of CD276/B7-H3 on T cells proliferation inhibition. We assessed CD276/B7-H3 expression by WJ-MSCs both in situ and alongside cell culture. WJ-MSCs were able to suppress T cell proliferation in mixed lymphocyte reaction (MLR). Moreover, we describe for the first time a specific role for CD276/B7-H3, since the immunomodulatory ability of WJ-MSCs was abolished upon anti-CD276/B7-H3 antibody addition to the MLR. These results further detail the immune regulation properties and tolerance induction exerted by human WJ-MSCs, in particular pointing to CD276/B7-H3 as one of the main involved factors. These data further suggest WJ-MSCs as potent tools to modulate local immune response in "support-type" regenerative medicine approaches.

• Klíčová slova
• B7-H3, CD276, Cell therapy, Human umbilical cord, Immunomodulation, Lymphocyte inhibition, Regenerative medicine, Stem cells, Wharton’s jelly mesenchymal stromal cells,
• MeSH
• aktivace lymfocytů imunologie   MeSH
• antigeny B7 antagonisté a inhibitory   imunologie   MeSH
• buněčná diferenciace * MeSH
• cytokiny imunologie   metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   imunologie   MeSH
• proliferace buněk MeSH
• pupečník cytologie   imunologie   MeSH
• techniky in vitro MeSH
• Whartonův rosol cytologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny B7 MeSH
• CD276 protein, human MeSH Prohlížeč
• cytokiny 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

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

INTRODUCTION: Crohn's disease (CD) is a disabling chronic enteropathy sustained by a harmful T-cell response toward antigens of the gut microbiota in genetically susceptible subjects. Growing evidence highlights the safety and possible efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this condition. Therefore, we aimed to investigate the effects of bone marrow-derived MSCs on pathogenic T cells with a view to clinical application. METHODS: T-cell lines from both inflamed and non-inflamed colonic mucosal specimens of CD patients and from healthy mucosa of control subjects were grown with the antigen muramyl-dipeptide in the absence or presence of donors' MSCs. The MSC effects were evaluated in terms of T-cell viability, apoptotic rate, proliferative response, immunophenotype, and cytokine profile. The role of the indoleamine 2,3-dioxygenase (IDO) was established by adding a specific inhibitor, the 1-methyl-DL-tryptophan, and by using MSCs transfected with the small interfering RNA (siRNA) targeting IDO. The relevance of cell-cell contact was evaluated by applying transwell membranes. RESULTS: A significant reduction in both cell viability and proliferative response to muramyl-dipeptide, with simultaneous increase in the apoptotic rate, was found in T cells from both inflamed and non-inflamed CD mucosa when co-cultured with MSCs and was reverted by inhibiting IDO activity and expression. A reduction of the activated CD4(+)CD25(+) subset and increase of the CD3(+)CD69(+) population were also observed when T-cell lines from CD mucosa were co-cultured with MSCs. In parallel, an inhibitory effect was evident on the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interferon-γ, interleukin-17A and -21, whereas that of the transforming growth factor-β and interleukin-6 were increased, and production of the tolerogenic molecule soluble HLA-G was high. These latter effects were almost completely eliminated by blocking the IDO, whose activity was upregulated in MSCs co-cultured with CD T cells. The use of a semipermeable membrane partially inhibited the MSC immunosuppressive effects. Finally, hardly any effects of MSCs were observed when T cells obtained from control subjects were used. CONCLUSION: MSCs exert potent immunomodulant effects on antigen-specific T cells in CD through a complex paracrine and cell-cell contact-mediated action, which may be exploited for widespread therapeutic use.

• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   MeSH
• antigeny povrchové metabolismus   MeSH
• apoptóza účinky léků   MeSH
• buňky kostní dřeně cytologie   MeSH
• časosběrné zobrazování MeSH
• Crohnova nemoc patologie   MeSH
• cytokiny metabolismus   MeSH
• dospělí MeSH
• HLA-G antigeny metabolismus   MeSH
• imunofenotypizace MeSH
• indolamin-2,3,-dioxygenasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• mezenchymální kmenové buňky cytologie   metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• proliferace buněk účinky léků   MeSH
• RNA interference MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• střevní sliznice cytologie   MeSH
• T-lymfocyty cytologie   účinky léků   imunologie   MeSH
• tryptofan analogy a deriváty   farmakologie   MeSH
• viabilita buněk MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-methyltryptophan MeSH Prohlížeč
• acetylmuramyl-alanyl-isoglutamin MeSH
• antigeny povrchové MeSH
• cytokiny MeSH
• HLA-G antigeny MeSH
• indolamin-2,3,-dioxygenasa MeSH
• malá interferující RNA MeSH
• tryptofan MeSH