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
BACKGROUND: In patients with colorectal liver metastases, the possibility for radical liver resection can be limited by oxaliplatin-induced sinusoidal obstruction syndrome (SOS). This study investigates the potential of mesenchymal stem cells (MSC) to improve the outcome of liver resections in pigs with SOS. MATERIALS AND METHODS: SOS was induced in all animals (n=20) on day 0. Animals in the experimental group (n=8) received allogeneic MSC on day 7. Liver resection was performed in all animals on day 14 and the animals were observed until day 28. Ultrasound volumetry, biochemical analysis and histological examination of liver parenchyma was performed during the follow-up period. RESULTS: Six animals from the control group died prematurely, while all animals survived in the experimental group. According to histology, biochemical analysis and ultrasound volumetry, there were no significant differences between the groups documenting the effect of MSC. CONCLUSION: Single dose allogeneic MSC administration improved survival of animals with SOS undergoing partial liver resection. Further experiments with different timing of liver resection and MSC administration should be performed to investigate the effect of MSC in more detail.
- Klíčová slova
- Sinusoidal obstruction syndrome, colorectal cancer, liver metastases, liver resection, mesenchymal stem cells, monocrotaline,
- MeSH
- biologické markery MeSH
- hepatektomie * metody MeSH
- imunofenotypizace MeSH
- imunohistochemie MeSH
- jaterní žilní okluze etiologie patologie terapie MeSH
- kolorektální nádory patologie MeSH
- kombinovaná terapie MeSH
- mezenchymální kmenové buňky * cytologie MeSH
- modely nemocí na zvířatech MeSH
- nádory jater komplikace sekundární MeSH
- prasata MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
The limited regenerative capacity of the heart after a myocardial infarct results in remodeling processes that can progress to congestive heart failure (CHF). Several strategies including mechanical stabilization of the weakened myocardium and regenerative approaches (specifically stem cell technologies) have evolved which aim to prevent CHF. However, their final performance remains limited motivating the need for an advanced strategy with enhanced efficacy and reduced deleterious effects. An epicardial carrier device enabling a targeted application of a biomaterial-based therapy to the infarcted ventricle wall could potentially overcome the therapy and application related issues. Such a device could play a synergistic role in heart regeneration, including the provision of mechanical support to the remodeling heart wall, as well as providing a suitable environment for in situ stem cell delivery potentially promoting heart regeneration. In this study, we have developed a novel, single-stage concept to support the weakened myocardial region post-MI by applying an elastic, biodegradable patch (SPREADS) via a minimal-invasive, closed chest intervention to the epicardial heart surface. We show a significant increase in %LVEF 14 days post-treatment when GS (clinical gold standard treatment) was compared to GS + SPREADS + Gel with and without cells (p ≤ 0.001). Furthermore, we did not find a significant difference in infarct quality or blood vessel density between any of the groups which suggests that neither infarct quality nor vascularization is the mechanism of action of SPREADS. The SPREADS device could potentially be used to deliver a range of new or previously developed biomaterial hydrogels, a remarkable potential to overcome the translational hurdles associated with hydrogel delivery to the heart.
- Klíčová slova
- Epicardial carrier device, Extravascular device, Hyaluronic acid hydrogel, Myocardial infarction, Stem cell delivery, Ventricular stabilization,
- MeSH
- biokompatibilní materiály MeSH
- buněčná a tkáňová terapie přístrojové vybavení metody MeSH
- design vybavení MeSH
- hydrogely aplikace a dávkování chemie farmakologie MeSH
- infarkt myokardu patofyziologie terapie MeSH
- kyselina hyaluronová MeSH
- lidé MeSH
- mezenchymální kmenové buňky * účinky léků MeSH
- perikard MeSH
- pohyb buněk účinky léků MeSH
- prasata MeSH
- transplantace mezenchymálních kmenových buněk MeSH
- tuková tkáň cytologie MeSH
- viskozita MeSH
- vstřebatelné implantáty * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- hydrogely MeSH
- kyselina hyaluronová MeSH
AIM: The therapeutic potential of adipose-derived stem cell conditioned medium (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI). METHODS: Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle tissue was collected 35 days after ischemia induction. Ischemic changes were evaluated in hematoxylin-eosin stained tissues for early (necrotic lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The expression of proangiogenic miR-126 was also evaluated using in situ hybridization. The levels of cytokines, insulin, and C-peptide were measured in blood. RESULTS: Early repair phases were observed more often in placebo-treated samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was not statistically significant. We demonstrated a statistically significant positive correlation between the early healing phases in tissue samples and C-peptide levels in peripheral blood. The expression of proangiogenic miR-126 was also shown in a number of structures in all phases of ischemic tissue healing. CONCLUSION: Based on our results, we believe that treatment with ASC-CM has the potential to accelerate the healing process in ischemic tissues in the rabbit model of CLI. The whole healing process was accompanied by miR-126 tissue expression. C-peptide could be used to monitor the course of the tissue healing process.
- Klíčová slova
- C-peptide, critical limb ischemia, cytokines, mesenchymal stem cells, miR-126, tissue healing,
- MeSH
- C-peptid krev MeSH
- cytokiny krev MeSH
- diabetická noha MeSH
- dospělí MeSH
- experimentální diabetes mellitus krev MeSH
- fibróza MeSH
- fyziologická neovaskularizace účinky léků MeSH
- granulační tkáň patologie MeSH
- hojení ran účinky léků fyziologie MeSH
- hybridizace in situ MeSH
- inzulin krev MeSH
- ischemie krev MeSH
- jizva patologie MeSH
- kosterní svaly krevní zásobení účinky léků patologie MeSH
- králíci MeSH
- kultivační média speciální farmakologie MeSH
- lidé MeSH
- mezenchymální kmenové buňky * MeSH
- mikro RNA metabolismus MeSH
- modely nemocí na zvířatech MeSH
- nekróza MeSH
- zadní končetina MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- králíci MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- C-peptid MeSH
- cytokiny MeSH
- inzulin MeSH
- kultivační média speciální MeSH
- mikro RNA MeSH
Diagnosing accessory breast tissue in a male patient is difficult when the condition is unilateral, and there is no areola or nipple. Pseudoangiomatous hyperplasia of the mammary stroma is an uncommon benign mesenchymal proliferation that may mimic low-grade angiosarcoma. We report herein an example of tumoriform pseudoangiomatous hyperplasia of the stroma arising in the accessory breast tissue of a 38-year-old man. The condition presented as a palpable tender axillary mass. Histopathologically, there were no changes of gynecomastia. Only two cases of pseudoangiomatous hyperplasia of the stroma have been previously reported in the accessory breast tissue of men showing unilateral or bilateral gynecomastia. Our case is the first report without associated gynecomastia. Radiologic imaging features are not sufficiently specific to enable a prospective diagnosis of pseudoangiomatous hyperplasia of the stroma. Microscopic examination of the lesion is indispensable in making a definitive diagnosis. Awareness of the condition can avoid difficulty in diagnosing it. Aberrant breast tissue with mass-forming pseudoangiomatous hyperplasia of the stroma, whilst rare, should be included among the benign proliferative mesenchymal lesions of the axilla. Keywords: aberrant breast tissue-accessory breast tissue-pseudoangiomatous stromal hyperplasia-gynecomastia-angiosarcoma-axilla.
- MeSH
- angiomatóza * diagnóza patologie MeSH
- axila MeSH
- buňky stromatu MeSH
- dospělí MeSH
- hyperplazie * diagnóza patologie MeSH
- lidé MeSH
- nemoci prsů * diagnóza patologie MeSH
- prospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Adipose/fat tissue provides an abundant source of stromal vascular fraction (SVF) cells for immediate administration and can also give rise to a substantial number of cultured, multipotent adipose-derived stromal cells (ADSCs). Recently, both SVF and ADSCs have gained wide-ranging translational significance in regenerative medicine. Initially used for cosmetic breast enhancement, this mode of treatment has found use in many diseases involving immune disorders, tissue degeneration, and ischaemic conditions. In this review, we try to address several important aspects of this field, outlining the biology, technology, translation, and challenges related to SVF- and ADSC-based therapies. Starting from the basics of SVF and ADSC isolation, we touch upon recently developed technologies, addressing elements of novel methods and devices under development for point-of-care isolation of SVF. Characterisation of SVF cells and ADSCs is also an evolving area and we look into unusual expression of CD34 antigen as an interesting marker for such purposes. Based on reports involving different cells of the SVF, we draw a potential mode of action, focussing on angiogenesis since it involves multiple cells, unlike immunomodulation which is governed predominantly by ADSCs. We have looked into the latest research, experimental therapies, and clinical trials which are utilising SVF/ADSCs in conditions such as multiple sclerosis, Crohn's disease, peripheral neuropathy, osteoarthritis, diabetic foot ulcer, and so forth. However, problems have arisen with regards to the lack of proper regulatory guidelines for such therapies and, since the introduction of US Food and Drug Administration draft guidelines and the Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act, the debate became more public with regards to safe and efficacious use of these cells.
- Klíčová slova
- CD34, Multipotent-stromal cells, Point-of-care biomedical devices, Regenerative medicine, Regulation of stem cell therapeutics, Stromal vascular fraction,
- MeSH
- buňky stromatu metabolismus patologie transplantace MeSH
- Crohnova nemoc metabolismus patologie terapie MeSH
- diabetická noha metabolismus patologie terapie MeSH
- lidé MeSH
- multipotentní kmenové buňky metabolismus patologie transplantace MeSH
- nemoci periferního nervového systému metabolismus patologie terapie MeSH
- osteoartróza metabolismus patologie terapie MeSH
- regenerativní lékařství metody MeSH
- roztroušená skleróza metabolismus patologie terapie MeSH
- tuková tkáň metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The cellular and molecular basis of vascular calcification (VC) in atherosclerosis is not fully understood. Here, we investigate role of resident/circulating progenitor cells in VC and contribution of inflammatory plaque environment to this process. Vessel-derived stem/progenitor cells (VSCs) and mesenchymal stem cells (MSCs) isolated from atherosclerotic ApoE(-/-) mice showed significantly more in vitro osteogenesis and chondrogenesis than cells generated from control C57BL/6 mice. To assess their ability to form bone in vivo, cells were primed chondrogenically or cultured in control medium on collagen glycosaminoglycan scaffolds in vitro prior to subcutaneous implantation in ApoE(-/-) and C57BL/6 mice using a crossover study design. Atherosclerotic ApoE(-/-) MSCs and VSCs formed bone when implanted in C57BL/6 mice. In ApoE(-/-) mice, these cells generated more mature bone than C57BL/6 cells. The atherosclerotic in vivo environment alone promoted bone formation by implanted C57BL/6 cells. Un-primed C57BL/6 VSCs were unable to form bone in either mouse strain. Treatment of ApoE(-/-) VSC chondrogenic cultures with interleukin (IL)-6 resulted in significantly increased glycosaminoglycan deposition and expression of characteristic chondrogenic genes at 21 days. In conclusion, resident vascular cells from atherosclerotic environment respond to the inflammatory milieu and undergo calcification. IL-6 may have a role in aberrant differentiation of VSCs contributing to vascular calcification in atherosclerosis.
- Klíčová slova
- Atherosclerosis, Chondrogenesis, Collagen scaffold, Endochondral ossification, In vivo, Mesenchymal stem cells, Pericytes, Vascular calcification, Vascular progenitor cells,
- MeSH
- apolipoproteiny E genetika MeSH
- aterosklerotický plát genetika patologie terapie MeSH
- ateroskleróza genetika patologie terapie MeSH
- buněčná diferenciace genetika MeSH
- cévy cytologie MeSH
- chondrogeneze genetika MeSH
- cytokiny metabolismus MeSH
- glykosaminoglykany metabolismus MeSH
- interleukin-6 metabolismus MeSH
- lidé MeSH
- mezenchymální kmenové buňky * MeSH
- myši MeSH
- osteogeneze genetika MeSH
- vaskulární kalcifikace genetika metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- apolipoproteiny E MeSH
- cytokiny MeSH
- glykosaminoglykany MeSH
- interleukin-6 MeSH
Adipose tissue is an abundant source of autologous adult stem cells that may bring new therapeutic perspectives on the treatment of diabetes and its complications. It is unclear whether adipose tissue-derived stromal cells (ASCs) of diabetic patients, constantly influenced by hyperglycaemia, have the same properties as non-diabetic controls. As an alternative source of ASCs, adipose tissue from distal limbs of diabetic patients with critical ischemia was isolated. ASCs were characterized in terms of cell surface markers, multilineage differentiation and the expression of vascular endothelial growth factor (VEGFA), chemokine-related genes and compared with non-diabetic controls. Flow cytometry analysis confirmed mesenchymal phenotypes in both diabetic and non-diabetic ASCs. Nevertheless, 40% of diabetic and 20% of non-diabetic ASC samples displayed high expressions of fibroblast marker, which inversely correlated with the expression of CD105. In diabetic patients, significantly decreased expression of VEGFA and chemokine receptor CXCR4 was found in fibroblast-positive ASCs, compared with their fibroblast-negative counterparts. Reduced osteogenic differentiation and the downregulation of chemokine CXCL12 were found in fibroblast-negative diabetic ASCs. Both diabetic and non-diabetic ASCs were differentiated into adipocytes and chondrocytes and did not reveal islet-like cell differentiation. According to this study, adipose tissue from distal limbs of diabetic patients is not satisfactory as an autologous ASC source. Hyperglycaemic milieu as well as other metabolic disorders linked to diabetes may have an influence on endogenous stem cell properties. The present study investigated the feasibility of autologous stem cell therapy in diabetic patients. ASCs isolated from the ischemic limb of diabetic patients were found to be less potent when compared phenotypically and functionally to control non-diabetic counterparts with no signs of limb ischemia. High expression of fibroblast markers associated with reduced expression of VEGFA as well as reduced osteogenic differentiation may have an impact on the effectiveness of autologous cell therapies in diabetic patients.
- Klíčová slova
- adipose tissue, cell therapy, diabetes, differentiation, flow cytometry, mesenchymal stem cells,
- MeSH
- biologické markery metabolismus MeSH
- buněčná diferenciace MeSH
- buňky stromatu cytologie metabolismus MeSH
- CD antigeny metabolismus MeSH
- chondrocyty cytologie metabolismus MeSH
- cytokiny metabolismus MeSH
- diabetes mellitus patologie MeSH
- diabetická noha patologie MeSH
- dospělí MeSH
- endoglin MeSH
- fibroblasty cytologie metabolismus MeSH
- ischemie patologie MeSH
- končetiny krevní zásobení patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezenchymální kmenové buňky cytologie metabolismus MeSH
- osteoblasty cytologie metabolismus MeSH
- podkožní tuk cytologie MeSH
- receptory buněčného povrchu metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tukové buňky cytologie metabolismus MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé 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
- biologické markery MeSH
- CD antigeny MeSH
- cytokiny MeSH
- endoglin MeSH
- ENG protein, human MeSH Prohlížeč
- receptory buněčného povrchu MeSH
- vaskulární endoteliální růstový faktor A MeSH