BACKGROUND: C-reactive protein (CRP) is an acute inflammatory protein detected in obese patients with metabolic syndrome. Moreover, increased CRP levels have been linked with atherosclerotic disease, congestive heart failure, and ischemic heart disease, suggesting that it is not only a biomarker but also plays an active role in the pathophysiology of cardiovascular diseases. Since endothelial dysfunction plays an essential role in various cardiovascular pathologies and is characterized by increased expression of cell adhesion molecules and inflammatory markers, we aimed to detect specific markers of endothelial dysfunction, inflammation, and oxidative stress in spontaneously hypertensive rats (SHR) expressing human CRP. This model is genetically predisposed to the development of the metabolic syndrome. METHODS: Transgenic SHR male rats (SHR-CRP) and non-transgenic SHR (SHR) at the age of 8 months were used. Metabolic profile (including serum and tissue triglyceride (TAG), serum insulin concentrations, insulin-stimulated incorporation of glucose, and serum non-esterified fatty acids (NEFA) levels) was measured. In addition, human serum CRP, MCP-1 (monocyte chemoattractant protein-1), and adiponectin were evaluated by means of ELISA, histological analysis was used to study morphological changes in the aorta, and western blot analysis of aortic tissue was performed to detect expression of endothelial, inflammatory, and oxidative stress markers. RESULTS: The presence of human CRP was associated with significantly decreased insulin-stimulated glycogenesis in skeletal muscle, increased muscle and hepatic accumulation of TAG and decreased plasmatic cGMP concentrations, reduced adiponectin levels, and increased monocyte chemoattractant protein-1 (MCP-1) levels in the blood, suggesting pro-inflammatory and presence of multiple features of metabolic syndrome in SHR-CRP animals. Histological analysis of aortic sections did not reveal any visible morphological changes in animals from both SHR and SHR-CRP rats. Western blot analysis of the expression of proteins related to the proper function of endothelium demonstrated significant differences in the expression of p-eNOS/eNOS in the aorta, although endoglin (ENG) protein expression remained unaffected. In addition, the presence of human CRP in SHR in this study did not affect the expression of inflammatory markers, namely p-NFkB, P-selectin, and COX2 in the aorta. On the other hand, biomarkers related to oxidative stress, such as HO-1 and SOD3, were significantly changed, indicating the induction of oxidative stress. CONCLUSIONS: Our findings demonstrate that CRP alone cannot fully induce the expression of endothelial dysfunction biomarkers, suggesting other risk factors of cardiovascular disorders are necessary to be involved to induce endothelial dysfunction with CRP.

• Klíčová slova
• Aorta, C-reactive protein, Endothelial dysfunction, Oxidative stress, Spontaneously hypertensive rat,
• MeSH
• adiponektin MeSH
• aorta MeSH
• biologické markery metabolismus   MeSH
• C-reaktivní protein metabolismus   MeSH
• chemokin CCL2 MeSH
• hypertenze * MeSH
• inzuliny * metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• metabolický syndrom * diagnóza   genetika   MeSH
• oxidační stres MeSH
• potkani inbrední SHR MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adiponektin MeSH
• biologické markery MeSH
• C-reaktivní protein MeSH
• chemokin CCL2 MeSH
• CRP protein, human MeSH Prohlížeč
• inzuliny * MeSH

BACKGROUND AND AIMS: Increased plasma levels of soluble endoglin (sEng) were detected in patients with endothelial dysfunction-related disorders and hypercholesterolemia. In this study, we hypothesized that high levels of sEng accompanied by mild hypercholesterolemia could aggravate endothelial and vessel wall dysfunction and affect endoglin/eNOS signaling in mouse aorta. METHODS: Three-month-old female transgenic mice on CBAxC57BL/6J background, with high levels of sEng (Sol-Eng+high HFD), and their littermates with low levels of sEng (Sol-Eng+low HFD), were fed a high fat diet for six months. Plasma samples were used for biochemical, ELISA and Luminex analyses of total cholesterol, sEng and inflammatory markers. Functional parameters of aorta were assessed with wire myograph 620M. Western blot analyses of membrane endoglin/eNOS signaling and endothelial dysfunction/inflammation markers in aorta were performed. RESULTS: Functional analysis of aorta showed impaired KCl induced vasoconstriction, endothelial-dependent relaxation after the administration of acetylcholine as well as endothelial-independent relaxation induced by sodium nitroprusside in the Sol-Eng+high HFD group compared to the Sol-Eng+low HFD group. Ach-induced vasodilation after administration of l-NAME was significantly higher in the Sol-Eng+high HFD group compared to the Sol-Eng+low HFD group. The expression of endoglin, p-eNOS/eNOS, pSmad2/3/Smad2/3 signaling pathway was significantly lower in the Sol-Eng+high HFD group compared to the Sol-Eng+low HFD group. CONCLUSIONS: The results indicate that long-term hypercholesterolemia combined with high levels of sEng leads to the aggravation of endothelial and vessel wall dysfunction in aorta, with possible alterations of the membrane endoglin/eNOS signaling, suggesting that high levels of soluble endoglin might be considered as a risk factor of cardiovascular diseases.

• Klíčová slova
• Endothelial dysfunction, Mice, Soluble endoglin, Vascular reactivity, eNOS,
• MeSH
• aorta metabolismus   patologie   patofyziologie   MeSH
• ateroskleróza genetika   metabolismus   patologie   patofyziologie   MeSH
• cévní endotel metabolismus   patologie   patofyziologie   MeSH
• dieta s vysokým obsahem tuků MeSH
• endoglin genetika   metabolismus   MeSH
• fosforylace MeSH
• hypercholesterolemie komplikace   etiologie   MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši inbrední CBA MeSH
• myši transgenní MeSH
• nemoci aorty genetika   metabolismus   patologie   patofyziologie   MeSH
• protein Smad2 metabolismus   MeSH
• protein Smad3 metabolismus   MeSH
• signální transdukce MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• upregulace MeSH
• vazodilatace MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endoglin MeSH
• ENG protein, human MeSH Prohlížeč
• mediátory zánětu MeSH
• Nos3 protein, mouse MeSH Prohlížeč
• protein Smad2 MeSH
• protein Smad3 MeSH
• Smad2 protein, mouse MeSH Prohlížeč
• Smad3 protein, mouse MeSH Prohlížeč
• synthasa oxidu dusnatého, typ III MeSH

AIMS: Endoglin is a transmembrane glycoprotein, that plays an important role in regulating endothelium. Proteolytic cleavage of membrane endoglin releases soluble endoglin (sEng), whose increased plasma levels have been detected in diseases related to the cardiovascular system. It was proposed that sEng might damage vascular endothelium, but detailed information about the potential mechanisms involved is not available. Thus, we hypothesized that sEng contributes to endothelial dysfunction, leading to a pro-inflammatory phenotype by a possible modulation of the TGF-β and/or inflammatory pathways. MAIN METHODS: Human umbilical vein endothelial cells (HUVECs) and Human embryonic kidney cell line (HEK293T) were treated with different sEng concentration and time in order to reveal possible effect on biomarkers of inflammation and TGF-β signaling. IL6 and NFκB reporter luciferase assays, quantitative real-time PCR analysis, Western blot analysis and immunofluorescence flow cytometry were used. KEY FINDINGS: sEng treatment results in activation of NF-κB/IL-6 expression, increased expression of membrane endoglin and reduced expression of Id-1. On the other hand, no significant effects on other markers of endothelial dysfunction and inflammation, including eNOS, peNOSS1177, VCAM-1, COX-1, COX-2 and ICAM-1 were detected. SIGNIFICANCE: As a conclusion, sEng treatment resulted in an activation of NF-κB, IL-6, suggesting activation of pro-inflammatory phenotype in endothelial cells. The precise mechanism of this activation and its consequence remains to be elucidated. A combined treatment of sEng with other cardiovascular risk factors will be necessary in order to reveal whether sEng is not only a biomarker of cardiovascular diseases, but also a protagonist of endothelial dysfunction.

• Klíčová slova
• Endothelial cells, IL-6, Inflammation, NF-κB, Soluble endoglin,
• MeSH
• endoglin biosyntéza   MeSH
• endoteliální buňky pupečníkové žíly (lidské) metabolismus   MeSH
• HEK293 buňky MeSH
• inhibitor diferenciace 1 biosyntéza   MeSH
• interleukin-6 biosyntéza   MeSH
• lidé MeSH
• NF-kappa B biosyntéza   MeSH
• regulace genové exprese * MeSH
• rozpustnost MeSH
• signální transdukce * MeSH
• zánět chemicky indukované   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endoglin MeSH
• ENG protein, human MeSH Prohlížeč
• ID1 protein, human MeSH Prohlížeč
• IL6 protein, human MeSH Prohlížeč
• inhibitor diferenciace 1 MeSH
• interleukin-6 MeSH
• NF-kappa B MeSH

Although prostate carcinoma (PCa) is by far the most commonly diagnosed neoplasia in men, corresponding diagnostic and therapeutic modalities have limited efficacy at present. Anticalins comprise a novel class of binding proteins based on a non-immunoglobulin scaffold that can be engineered to specifically address molecular targets of interest. Here we report the selection and characterization of Anticalins that recognize human prostate-specific membrane antigen (PSMA), a membrane-tethered metallopeptidase constituting a disease-related target for imaging and therapy of PCa as well as solid malignancies in general. We used a randomized lipocalin library based on the human lipocalin 2 (Lcn2) scaffold together with phage display and ELISA screening to select PSMA-specific variants. Five Anticalin candidates from the original panning were expressed in Escherichia coli as soluble monomeric proteins, revealing affinities toward PSMA down to the low nanomolar range. Binding characteristics of the most promising candidate were further improved via affinity maturation by applying error-prone PCR followed by selection via phage display as well as bacterial surface display under more stringent conditions. In BIAcore measurements, the dissociation constant of the best Anticalin was determined as ∼500 pM, with a substantially improved dissociation rate compared with the first-generation candidate. Finally, immunofluorescence microscopy revealed specific staining of PSMA-positive tumor cell lines while flow cytometric analysis confirmed the ability of the selected Anticalins to detect PSMA on live cells. Taken together, Anticalins resulting from this study offer a viable alternative to antibody-based PSMA binders for biomedical applications, including in vivo imaging of PCa or neovasculature of solid tumors.

• Klíčová slova
• Anticalin, glutamate carboxypeptidase II, lipocalin, non-immunoglobulin scaffold, prostate carcinoma,
• MeSH
• antigeny povrchové chemie   metabolismus   MeSH
• ELISA MeSH
• glutamátkarboxypeptidasa II chemie   metabolismus   MeSH
• lidé MeSH
• lipokaliny genetika   metabolismus   MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• mutace MeSH
• proteinové inženýrství * MeSH
• sekvence aminokyselin MeSH
• terciární struktura proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny povrchové MeSH
• FOLH1 protein, human MeSH Prohlížeč
• glutamátkarboxypeptidasa II MeSH
• lipokaliny MeSH

Soluble endoglin (sEng) released into the circulation was suggested to be related to cardiovascular based pathologies. It was demonstrated that a combination of high sEng levels and long-term exposure (six months) to high fat diet (HFD) resulted in aggravation of endothelial dysfunction in the aorta. Thus, in this study, we hypothesized that a similar experimental design would affect the heart morphology, TGFβ signaling, inflammation, fibrosis, oxidative stress and eNOS signaling in myocardium in transgenic mice overexpressing human sEng. Three-month-old female transgenic mice overexpressing human sEng in plasma (Sol-Eng+ high) and their age-matched littermates with low levels of human sEng (Sol-Eng+ low) were fed a high-fat diet containing 1.25% of cholesterol and 40% of fat for six months. A blood analysis was performed, and the heart samples were analyzed by qRT-PCR and Western blot. The results of this study showed no effects of sEng and HFD on myocardial morphology/hypertrophy/fibrosis. However, the expression of pSmad2/3 and p-eNOS was reduced in Sol-Eng+ high mice. On the other hand, sEng and HFD did not significantly affect the expression of selected members of TGFβ signaling (membrane endoglin, TGFβRII, ALK-5, ALK-1, Id-1, PAI-1), inflammation (VCAM-1, ICAM-1), oxidative stress (NQO1, HO-1) and heart remodeling (PDGFβ, COL1A1, β-MHC). In conclusion, the results of this study confirmed that sEng, even combined with a high-fat diet inducing hypercholesterolemia administered for six months, does not affect the structure of the heart with respect to hypertrophy, fibrosis, inflammation and oxidative stress. Interestingly, pSmad2/3/p-eNOS signaling was reduced in both the heart in this study and the aorta in the previous study, suggesting a possible alteration of NO metabolism caused by six months exposure to high sEng levels and HFD. Thus, we might conclude that sEng combined with a high-fat diet might be related to the alteration of NO production due to altered pSmad2/3/p-eNOS signaling in the heart and aorta.

• MeSH
• aorta metabolismus   patologie   MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• endoglin * krev   metabolismus   MeSH
• fibróza MeSH
• hypercholesterolemie metabolismus   MeSH
• hypertrofie MeSH
• myokard metabolismus   patologie   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endoglin * MeSH
• ENG protein, human MeSH Prohlížeč
• oxid dusnatý MeSH

Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system. High concentration of sEng was also proposed to contribute to the development of endothelial dysfunction, but there is no direct evidence to support this hypothesis. Therefore, in the present work we analyzed whether high sEng levels induce endothelial dysfunction in aorta by using transgenic mice with high expression of human sEng. Transgenic mice with high expression of human sEng on CBAxC57Bl/6J background (Sol-Eng+) and age-matched transgenic littermates that do not develop high levels of human soluble endoglin (control animals in this study) on chow diet were used. As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals. Functional analysis either in vivo or ex vivo in isolated aorta demonstrated that the endothelium-dependent vascular function was similar in Sol-Eng+ and control mice. In addition, Western blot analysis showed no differences between Sol-Eng+ and control mice in the protein expression levels of endoglin, endothelial NO-synthase (eNOS) and pro-inflammatory ICAM-1 and VCAM-1 from aorta. Our results demonstrate that high levels of soluble endoglin alone do not induce endothelial dysfunction in Sol-Eng+ mice. However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.

• MeSH
• aorta MeSH
• arteriální tlak fyziologie   MeSH
• cévní buněčněadhezivní molekula-1 metabolismus   MeSH
• cévní endotel metabolismus   patologie   MeSH
• endoglin MeSH
• intracelulární signální peptidy a proteiny krev   MeSH
• kardiovaskulární nemoci krev   metabolismus   patologie   MeSH
• mezibuněčná adhezivní molekula-1 metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cévní buněčněadhezivní molekula-1 MeSH
• endoglin MeSH
• Eng protein, mouse MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• mezibuněčná adhezivní molekula-1 MeSH
• Nos3 protein, mouse MeSH Prohlížeč
• synthasa oxidu dusnatého, typ III MeSH

Pulsatile Carmat bioprosthetic total artificial heart (C-TAH) is designed to be implanted in patients with biventricular end-stage heart failure. Since flow variation might contribute to endothelial dysfunction, we explored circulating endothelial biomarkers after C-TAH implantation in seven patients and compared the manual and autoregulated mode. Markers of endothelial dysfunction and regeneration were compared before and during a 6- to 9-month follow-up after implantation. The follow-up was divided into three periods (< 3, 3-6, and > 6 months) and used to estimate the temporal trends during the study period. A linear mixed model was used to analyze repeated measures and association between tested parameters according to the mode of C-TAH and the time. Relevance of soluble endoglin (sEndoglin) level increase has been tested on differentiation and migration potential of human vasculogenic progenitor cells (endothelial colony forming cells [ECFCs]). Normal sEndoglin and soluble endothelial protein C receptor (sEPCR) levels were found in patients after implantation with autoregulated C-TAH, whereas they significantly increased in the manual mode, as compared with pretransplant values (p = 0.005 and 0.001, respectively). In the autoregulated mode, a significant increase in the mobilization of cytokine stromal cell-derived factor 1 was found (p = 0.03). After adjustment on the mode of C-TAH, creatinine or C-reactive protein level, sEndoglin, and sEPCR, were found significantly associated with plasma total protein levels. Moreover, a significant decrease in pseudotubes formation and migration ability was observed in vitro in ECFCs receiving sEndoglin activation. Our combined analysis of endothelial biomarkers confirms the favorable impact of blood flow variation achieved with autoregulation in patients implanted with the bioprosthetic total artificial heart.

• MeSH
• biologické markery analýza   MeSH
• bioprotézy * MeSH
• endoglin analýza   MeSH
• endotel patologie   MeSH
• endoteliální receptor proteinu C analýza   MeSH
• homeostáza MeSH
• lidé MeSH
• následné studie MeSH
• senioři MeSH
• srdeční selhání terapie   MeSH
• umělé srdce * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• endoglin MeSH
• endoteliální receptor proteinu C MeSH
• ENG protein, human MeSH Prohlížeč

Erectile dysfunction (ED) and diabetes mellitus (DM) share common pathophysiological risk factors including endothelial dysfunction which together with hyperglycemia contribute to the increased oxidative/glycooxidative stress. A reduced NO concentration is insufficient for relaxation processes in the penis. Chronic inflammation and endoglin are involved in the regulation of endothelial function. Adiponectin from the adipose tissue has anti-inflammatory effects. Our study aimed to investigate the relation between erectile function in patients with and without DM and the oxidative stress, hormone adiponectin, and endothelial dysfunction marker endoglin. Men (n=32) with ED evaluated by the International Index of Erectile function (IIEF-5) questionnaire (17 without DM (NDM); 15 with type 2 diabetes mellitus (DM)) and 31 controls were included. Advanced glycation end products (AGEs), 8-isoprostanes (8-isoP), protein carbonyls, antioxidant capacity, adiponectin and endoglin were determined in the blood. DM patients compared to NDM patients and controls, had increased levels of glucose, C-reactive protein, triacylglycerols, 8-isoP, AGEs, endoglin and BMI. IIEF-5 score, NO and adiponectin levels were decreased. We are the first to find out that endoglin shows a negative correlation with erectile function in NDM, but not in DM patients. Endoglin can be considered as endothelial dysfunction marker in nondiabetic men suffering from ED.

• MeSH
• adiponektin krev   MeSH
• diabetes mellitus 2. typu krev   diagnóza   epidemiologie   MeSH
• dospělí MeSH
• endoglin krev   MeSH
• erektilní dysfunkce krev   diagnóza   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• oxidační stres fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• adiponektin MeSH
• ADIPOQ protein, human MeSH Prohlížeč
• endoglin MeSH
• ENG protein, human MeSH Prohlížeč

AIMS: A soluble form of endoglin (sEng) was proposed to participate in the induction of endothelial dysfunction in small blood vessels. Here, we tested the hypothesis that high levels of sEng combined with a high-fat diet induce endothelial dysfunction in an atherosclerosis-prone aorta. METHODS AND RESULTS: Six-month-old female and male transgenic mice overexpressing human sEng (Sol-Eng+) with low (Sol-Eng+low) or high (Sol-Eng+high) levels of plasma sEng were fed a high-fat rodent diet containing 1.25% cholesterol and 40% fat for 3 months. The plasma cholesterol and mouse sEng levels did not differ in the Sol-Eng+high and Sol-Eng+low mice. The expression of proinflammatory (P-selectin, ICAM-1, pNFκB and COX-2) and oxidative-stress-related markers (HO-1, NOX-1 and NOX-2) in the aortas of Sol-Eng+high female mice was significantly higher than in Sol-Eng+low female mice. Endothelium-dependent vasodilatation induced by acetylcholine was preserved better in the Sol-Eng+ high female mice than in the Sol-Eng+low female mice. CONCLUSION: These results suggest that high concentrations of sEng in plasma in combination with a high-fat diet induce the simultaneous activation of proinflammatory, pro-oxidative and vasoprotective mechanisms in mice aorta and the balance of these biological processes determines whether the final endothelial phenotype is adaptive or maladaptive.

• MeSH
• aorta účinky léků   metabolismus   patofyziologie   MeSH
• ateroskleróza krev   genetika   metabolismus   patofyziologie   MeSH
• biologické markery metabolismus   MeSH
• dieta s vysokým obsahem tuků * MeSH
• endoglin krev   genetika   metabolismus   MeSH
• fenotyp MeSH
• fyziologická adaptace MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši inbrední CBA MeSH
• myši transgenní MeSH
• nemoci aorty krev   genetika   metabolismus   patofyziologie   MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres * MeSH
• upregulace MeSH
• vazodilatace * účinky léků   MeSH
• vazodilatancia farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zánět krev   genetika   metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• endoglin MeSH
• ENG protein, human MeSH Prohlížeč
• mediátory zánětu MeSH
• oxid dusnatý MeSH
• vazodilatancia MeSH

Bone marrow and adipose tissue human mesenchymal stem cells were seeded in highly performing 3D gelatin-chitosan hybrid hydrogels of varying chitosan content in the presence of human platelet lysate and evaluated for their proliferation and osteogenic differentiation. Both bone marrow and adipose tissue human mesenchymal stem cells in gelatin-chitosan hybrid hydrogel 1 (chitosan content 8.1%) or gelatin-chitosan hybrid hydrogel 2 (chitosan 14.9%) showed high levels of viability (80%-90%), and their proliferation and osteogenic differentiation was significantly higher with human platelet lysate compared to fetal bovine serum, particularly in gelatin-chitosan hybrid hydrogel 1. Mineralization was detected early, after 21 days of culture, when human platelet lysate was used in the presence of osteogenic stimuli. Proteomic characterization of human platelet lysate highlighted 59 proteins mainly involved in functions related to cell adhesion, cellular repairing mechanisms, and regulation of cell differentiation. In conclusion, the combination of our gelatin-chitosan hybrid hydrogels with hPL represents a promising strategy for bone regenerative medicine using human mesenchymal stem cells.

• Klíčová slova
• Hybrid chitosan-gelatin hydrogel, bone regeneration, human mesenchymal stem cells, human platelet lysate, tissue engineering,
• Publikační typ
• časopisecké články MeSH