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1.
Eklem Hastalik Cerrahisi ; 30(3): 289-95, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31650927

RESUMO

OBJECTIVES: This study aims to assess the effects of the hematopoietic stem cells and endothelial progenitor cells in peripheral blood and monocyte cluster of differentiation (CD) 34, CD133 and CD309 expression levels on maturation at the repair site in patients who underwent forearm arterial repair. PATIENTS AND METHODS: This prospective study included 30 patients (23 males, 7 females; mean age 28.9±1.8 years; range, 18 to 49 years) with a well-defined cut at the wrist due to a stabbing injury but no comorbid condition who presented to the emergency department of our hospital between November 2014 and November 2017. Vascular patency was assessed by Doppler sonography in patients who underwent forearm arterial repair via micro-vascular techniques. The relationships between patency and hematopoietic stem and endothelial progenitor cell markers such as CD34, CD133 and CD309 were assessed by flow cytometry. RESULTS: The patients were divided into two groups according to presence of sufficient flow in the arteries repaired. The mean CD34 expression level was 72.09±3.00 in the group with maturation whereas it was 54.64±7.34 in the group without maturation, indicating a statistically significant difference (p<0.05). In addition, the likelihood of sufficient flow was increased by 1.075 per one unit increase in CD34 level. Resistive index values were significantly lower in the group with maturation and CD34 level was predictive for maturation of arterial repair. CONCLUSION: In the present study, the findings demonstrated that high CD34 expression level has favorable effects on maturation after arterial repair.


Assuntos
Células Progenitoras Endoteliais/fisiologia , Antebraço/irrigação sanguínea , Células-Tronco Hematopoéticas/fisiologia , Artéria Radial/lesões , Adolescente , Adulto , Biomarcadores , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Artéria Radial/fisiopatologia , Artéria Radial/cirurgia , Ferimentos Perfurantes/fisiopatologia , Traumatismos do Punho/fisiopatologia , Adulto Jovem
2.
Respir Res ; 20(1): 131, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242908

RESUMO

BACKGROUND: Patients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model. METHODS: LPS was used to induce ALI in mice, and then the mice received intraperitoneal injections of Rev-D4F. Immunohistochemical staining, flow cytometry, MTT, transwell, and western blotting were used to assess the effect of Rev-D4F on repairment of lung impairment, and improvement of EPC numbers and function, as well as the signaling pathways involved. RESULTS: Rev-D4F inhibits LPS-induced pulmonary edema and decreases plasma levels of the pro-inflammatory mediators TNF-α and ET-1 in ALI mice. Rev-D4F inhibited infiltration of red and white blood cells into the interstitial space, reduced lung injury-induced inflammation, and restored injured pulmonary capillary endothelial cells. In addition, Rev-D4F increased numbers of circulating EPC, stimulated EPC differentiation, and improved EPC function impaired by LPS. Rev-D4F also acted via a PI3-kinase-dependent mechanism to restore levels of phospho-AKT, eNOS, and phospho-eNOS suppressed by LPS. CONCLUSIONS: These findings indicate that Rev-D4F has an important vasculoprotective role in ALI by improving the EPC numbers and functions, and Rev-D4F reverses LPS-induced EPC dysfuncion partially through PI3K/AKT/eNOS signaling pathway.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Células Progenitoras Endoteliais/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Peptídeos/uso terapêutico , Lesão Pulmonar Aguda/metabolismo , Animais , Relação Dose-Resposta a Droga , Células Progenitoras Endoteliais/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/farmacologia
3.
Phytomedicine ; 61: 152850, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31035054

RESUMO

BACKGROUD: Endothelial progenitor cells (EPCs) have been characterized as one of the key effectors of endothelial healing. The effect of Danhong injection (DHI), the most widely prescribed Chinese medicine for coronary heart disease (CHD), on EPCs mobilization remains unclear. PURPOSE: We aimed to assess the effect of DHI on EPCs mobilization to repair percutaneous coronary intervention (PCI) induced vascular injury, and to investigate the characteristics and potential mechanism of DHI on EPCs mobilization. METHOD: Forty-two patients with CHD underwent PCI and received stent implantation were enrolled in a Phase II clinical trials. All patients received routine western medical treatment after PCI, patients of DHI group received DHI in addition. The levels of CECs, cytokines (vWF, IL-6, CRP) and EPCs were analyzed at baseline, post-PCI and after treatment. To investigate the characteristics of DHI on EPCs mobilization, 12 healthy volunteers received intravenous infusion of DHI once and the other 12 received for 7 days. EPCs enumeration were done at a series of time points. At last we tested the effect of DHI and three chemical constituents of DHI (danshensu; lithospermic acid, LA; salvianolic acid D, SaD) on EPCs level and expression of Akt, eNOS and MMP-9 in bone marrow cells of myocardial infarction (MI) mice. RESULTS: In the DHI group the angina symptoms were improved, the levels of cytokines and CECs were reduced; while EPCs population was increased after treatment. In the phase I clinical trials, EPCs counts reached a plateau phase in 9 h and maintained for more than 10 h after a single dose. After continuous administration, EPCs levels plateaued on the 3rd or 4th day, and maintain till 1 day after the withdrawal, then its levels gradually declined. DHI treatment induced a timely dependent mobilization of EPCs. DHI promoted EPCs mobilization via upregulating the expression of Akt, eNOS and MMP-9 in BM. LA and SaD have played a valuable role in EPCs mobilization. CONCLUSION: These initial results demonstrated that DHI is effective in alleviating endothelial injury and promoting endothelial repair through enhancing EPCs mobilization and revealed the effect feature and possible mechanisms of DHI in mobilizing EPCs.


Assuntos
Fármacos Cardiovasculares/farmacologia , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/cirurgia , Medicamentos de Ervas Chinesas/farmacologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Endotélio Vascular/lesões , Idoso , Animais , Fármacos Cardiovasculares/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Células Progenitoras Endoteliais/fisiologia , Feminino , Humanos , Injeções , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Óxido Nítrico Sintase Tipo III/metabolismo , Intervenção Coronária Percutânea/efeitos adversos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lesões do Sistema Vascular/tratamento farmacológico , Lesões do Sistema Vascular/etiologia
4.
Int J Oncol ; 54(4): 1327-1336, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30968151

RESUMO

Endothelial progenitor cells (EPCs) are bone marrow (BM)­derived progenitor cells that can differentiate into mature endothelial cells, contributing to vasculogenesis in the blood vessel formation process. Runt­related transcription factor 3 (RUNX3) belongs to the Runt domain family and is required for the differentiation of specific immune cells and neurons. The tumor suppressive role of RUNX3, via the induction of apoptosis and cell cycle arrest in a variety of cancers, and its deletion or frequent silencing by epigenetic mechanisms have been studied extensively; however, its role in the differentiation of EPCs is yet to be investigated. Therefore, in the present study, adult BM­derived hematopoietic stem cells (HSCs) were isolated from Runx3 heterozygous (Rx3+/­) or wild­type (WT) mice. The differentiation of EPCs from the BM­derived HSCs of Rx3+/­ mice was found to be significantly increased compared with those of the WT mice, as determined by the number of small or large colony­forming units. The migration and tube formation abilities of Rx3+/­ EPCs were also observed to be significantly increased compared with those of WT EPCs. Furthermore, the number of circulating EPCs, defined as CD34+/vascular endothelial growth factor receptor 2 (VEGFR2)+ cells, was also significantly increased in Rx3+/­ mice. Hypoxia­inducible factor (HIF)­1α was upregulated in Rx3+/­ EPCs compared with WT EPCs, even under normoxic conditions. Furthermore, in a hindlimb ischemic mouse models, the recovery of blood flow was observed to be highly stimulated in Rx3+/­ mice compared with WT mice. Also, in a Lewis lung carcinoma cell allograft model, the tumor size in Rx3+/­ mice was significantly larger than that in WT mice, and the EPC cell population (CD34+/VEGFR2+ cells) recruited to the tumor was greater in the Rx3+/­ mice compared with the WT mice. In conclusion, the present study revealed that Runx3 inhibits vasculogenesis via the inhibition of EPC differentiation and functions via the suppression of HIF­1α activity.


Assuntos
Carcinoma Pulmonar de Lewis/patologia , Diferenciação Celular/fisiologia , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Células Progenitoras Endoteliais/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Animais , Vasos Sanguíneos/crescimento & desenvolvimento , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Membro Posterior/irrigação sanguínea , Humanos , Isquemia/patologia , Masculino , Camundongos , Camundongos Transgênicos , Neovascularização Patológica/patologia , Cultura Primária de Células , Regulação para Cima
5.
Plast Reconstr Surg ; 143(4): 744e-755e, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30921123

RESUMO

BACKGROUND: Fat grafting has become a valuable technique for soft-tissue reconstruction; however, long-lasting success depends on several determinants. An early blood supply to the transplanted adipocytes is important to prevent ischemia. The recently developed quality and quantity (QQ) culture increases the vasculogenic potential of endothelial progenitor cells. The authors used a murine fat grafting model to address the hypothesis that QQ-cultured endothelial progenitor cells stimulate the establishment of a blood vessel network and increase graft success. METHODS: c-KitSca-1Lin (KSL) cells were isolated as endothelial progenitor cell precursors from C57BL/6 mice. Adipose tissue was grafted with QQ-cultured KSL cells (QQKSL group), uncultured KSL cells (KSL group), adipose-derived stem cells (ASC group), and a combination (QQKSL+ASC group), and compared to a control group. Five and 10 weeks later, grafts were weighed, histologic and immunohistochemical parameters were evaluated, and gene expression was quantified by quantitative polymerase chain reaction. RESULTS: The highest vessel density was observed in the combined QQKSL+ASC group (68.0 ± 4.3/mm; p < 0.001) and the QQKSL group (53.9 ± 3.0/mm; p < 0.001). QQKSL cells were engrafted in proximity to the graft vasculature. QQKSL cells decreased the fibrosis percentage (13.8 ± 1.8 percent; p < 0.05). The combined QQKSL+ASC group (22.4 ± 1.8/mm; p < 0.001) showed the fewest local inflammation units. A significant up-regulation of platelet-derived growth factor and adiponectin expression was observed in the QQKSL group and QQKSL+ASC group. Graft weight persistence was not significantly different between groups. CONCLUSIONS: Supplementing fat grafts with quality and quantity-cultured endothelial progenitor cells improves graft quality by stimulating vascularization. The increased vessel density is associated with less fibrosis, less inflammation, and better adipose tissue integrity. Enriching fat grafts with QQ-cultured endothelial progenitor cells is a potential solution to their clinical shortcomings.


Assuntos
Tecido Adiposo/transplante , Células Progenitoras Endoteliais/fisiologia , Neovascularização Fisiológica/fisiologia , Tecido Adiposo/patologia , Animais , Células Cultivadas , Aloenxertos Compostos/irrigação sanguínea , Modelos Animais de Doenças , Fibrose/patologia , Sobrevivência de Enxerto/fisiologia , Camundongos Endogâmicos C57BL
6.
Biomed Pharmacother ; 111: 1088-1102, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841422

RESUMO

This study tested whether sitagliptin and shock wave (SW)-assisted circulatory-derived autologous endothelial progenitor cell (EPC) therapy would effectively preserve residual renal function in chronic kidney disease (CKD) induced by 5/6 left-nephrectomy/remove right kidney plus daily feeding high-protein diet (HPD) in rat. Adult-male SD rats (n = 40) were categorized into group 1 (sham-operated control with HPD), group 2 (HPD-CKD), group 3 [HPD-CKD + EPC (1.2 × 106 cell)/intra-vessel administration by day 14 after CKD-induction], group 4 [HPD-CKD + SW (0.12 mJ/mm2/180 shorts) at days 14/21/28 after CKD-induction by ultrasound-guided application] and group 5 [HPD-CKD + SW + EPC + sitagliptin (Sita; 600 mg/kg/day since day 14 after CKD induction)]. All animals were euthanized by day 60. By day 60, renal blood flow (RBF) was highest in group 1 and progressively increased from groups 2 to 5, whereas the levels of creatinine/BUN/proteinuria exhibited an opposite pattern of RBF among the five groups (all p < 0.001). The circulating levels of GLP-1/SDF-1α and protein levels of angiogenesis (VEGF/SDF-1α/CXCR4) and GLP-1R in kidney were progressively increased from groups 1 to 5, whereas circulating DPP4 activity exhibited an opposite pattern of SDF-1α among the groups (all p < 0.0001). The protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptosis (Bax/caspase-3/PARP), fibrosis (Smad3/TGF-ß) and inflammation (TNF-α/NF-κB/MMP-2) and kidney injury score displayed an opposite pattern, whereas the protein expressions of TMP2, endothelial-cell markers (CD31/eNOS) and podocyte integrity biomarkers (podocin/ZO-1/synaptopodin) exhibited an identical pattern of RBF among the groups (all p < 0.001). In conclusion Sita associated SW-assisted EPC effectively protected residual renal function in CKD.


Assuntos
Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Células Progenitoras Endoteliais/fisiologia , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Fosfato de Sitagliptina/farmacologia , Animais , Biomarcadores/metabolismo , Terapia Baseada em Transplante de Células e Tecidos/métodos , Creatinina/metabolismo , Células Progenitoras Endoteliais/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipoglicemiantes/farmacologia , Rim/metabolismo , Rim/fisiopatologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Proteinúria/metabolismo , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia
7.
Acta Diabetol ; 56(7): 785-795, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30859314

RESUMO

AIMS: Circulating endothelial progenitor cells (EPCs) play a key role in maintaining endothelial function. Dysfunction of EPCs is associated with the cardiovascular complication of diabetes. The purpose of this study is to investigate the direct effects of hyperinsulinemia on EPCs and the underlying mechanisms. METHODS: EPCs isolated from healthy adults were cultured with various concentrations of insulin (control group, without insulin; physiological insulin group, 10 nM insulin and hyperinsulinemia group, 100 nM insulin) with or without phosphatidylinositol-3-kinase (PI3-K) inhibitor (LY294002, 5 µM), endothelial nitric oxide synthase (eNOS) inhibitor (L-NG-nitro-arginine methyl ester (L-NAME), 100 µM), sodium nitroprusside (SNP, 25 µM), p38 mitogen-activated protein kinase(MAPK) inhibitor (SB203580, 5 µM) or extracellular signal-regulated kinases (ERK) 1/2 inhibitor (PD98059, 10 µM). Proliferation, tube formation, and apoptosis of EPCs were determined. Expressions of eNOS, PI3-K, protein kinase B (Akt), p38 MAPK, and ERK 1/2 were assessed. RESULTS: Hyperinsulinemia caused a significant decrease in proliferation and tube formation abilities than control group. Hyperinsulinemia increased apoptosis rate of EPCs than control group. Furthermore, hyperinsulinemia downregulated phosphorylation of eNOS, PI3-K and Akt, and upregulated phosphorylation of p38 MAPK and ERK. SNP could restore impaired tube formation induced by hyperinsulinemia. P38 MAPK inhibitor but not ERK inhibitor could decrease apoptosis induced by hyperinsulinemia. CONCLUSION: Hyperinsulinemia impaired EPCs' tube formation ability by downregulation of PI-3K/Akt/eNOS pathway. Hyperinsulinemia induced apoptosis of EPCs via upregulation of p38 MAPK.


Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/fisiologia , Hiperinsulinismo/fisiopatologia , Insulina/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Adulto , Animais , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Progenitoras Endoteliais/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/patologia , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Transdução de Sinais/efeitos dos fármacos
8.
Pharmacol Res Perspect ; 7(1): e00451, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30598826

RESUMO

We investigated whether combination therapy of G-CSF and erythropoietin (EPO)-liposome with Siaryl Lewis X (SLX) is more cardioprotective than G-CSF or EPO-liposome with SLX alone. For the purpose of generating myocardial infarction (MI), rabbits underwent 30 minutes of coronary occlusion and 14 days of reperfusion. We administered saline (control group, i.v.,), G-CSF (G group, 10 µg/kg/day × 5 days, i.c., starting at 24 hours after reperfusion), EPO-liposome with SLX (LE group, i.v., 2500 IU/kg EPO containing liposome with SLX, immediately after reperfusion), and G-CSF + EPO-liposome with SLX (LE + G group) to the rabbits. The MI size was the smallest in the LE+G group (14.7 ± 0.8%), and smaller in the G group (22.4 ± 1.5%) and LE group (18.5 ± 1.1%) than in the control group (27.8 ± 1.5%). Compared with the control group, the cardiac function and remodeling of the G, LE, and LE + G groups were improved, and LE + G group tended to show the best improvement. The number of CD31-positive microvessels was the greatest in the LE + G group, greater in the G and LE groups than in the control group. Higher expressions of phosphorylated (p)-Akt and p-ERK were observed in the ischemic area of the LE and LE + G groups. The number of CD34+/CXCR4+ cells was significantly higher in the G and LE + G groups. The cardiac SDF-1 was more expressed in the G and LE + G groups. In conclusion, Post-MI combination therapy with G-CSF and EPO-liposome with SLX is more cardioprotective than G-CSF or EPO-liposome with SLX alone through EPCs mobilization, neovascularization, and activation of prosurvival signals.


Assuntos
Células Progenitoras Endoteliais/fisiologia , Eritropoetina/farmacologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Vasos Coronários/citologia , Vasos Coronários/efeitos dos fármacos , Modelos Animais de Doenças , Composição de Medicamentos/métodos , Quimioterapia Combinada/métodos , Ecocardiografia , Células Progenitoras Endoteliais/efeitos dos fármacos , Eritropoetina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Coração/efeitos dos fármacos , Lipossomos , Masculino , Microvasos/citologia , Microvasos/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Neovascularização Fisiológica/efeitos dos fármacos , Oligossacarídeos/química , Coelhos , Regeneração/efeitos dos fármacos , Resultado do Tratamento
9.
PLoS One ; 14(1): e0210198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682162

RESUMO

Various cell-based therapeutic strategies have been investigated for vascular and tissue regeneration after ischemic stroke. We have developed a novel cell population, called regeneration-associated cells (RACs), by quality- and quantity-controlled culture of unfractionated mononuclear cells. RACs were trans-arterially injected into 10-week-old syngeneic male mice at 1, 3, 5 or 7 days after permanent middle cerebral artery occlusion (MCAO) to determine the optimal timing for administration in terms of outcome at day 21. Next, we examined the effects of RACs injection at day 1 after MCAO on neurological deficits, infarct volume, and mediators of vascular regeneration and anti-inflammation at days 7 and 21. Infarct volume at day 21 was significantly reduced by transplantation of RACs at day 1 or 3. RACs injected at day 1 reduced the infarct volume at day 7 and 21. Angiogenesis and anti-inflammatory mediators, VEGF and IL-10, were increased at day 7, and VEGF was still upregulated at day 21. We also observed significantly enhanced ink perfusion in vivo, tube formation in vitro, and definitive endothelial progenitor cell colonies in colony assay. These results suggest that RAC transplantation in MCAO models promoted significant recovery of neural tissues through intensified anti-inflammatory and angiogenic effects.


Assuntos
Cérebro/irrigação sanguínea , Células Progenitoras Endoteliais/transplante , Infarto da Artéria Cerebral Média/terapia , Neovascularização Fisiológica/fisiologia , Regeneração , Indutores da Angiogênese , Proteínas Angiogênicas/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Cérebro/patologia , Meios de Cultura/metabolismo , Modelos Animais de Doenças , Células Progenitoras Endoteliais/fisiologia , Humanos , Infarto da Artéria Cerebral Média/etiologia , Infarto da Artéria Cerebral Média/patologia , Leucócitos Mononucleares/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Artéria Cerebral Média/cirurgia , Cultura Primária de Células/métodos , Resultado do Tratamento
10.
Colloids Surf B Biointerfaces ; 174: 587-597, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30504039

RESUMO

We report a multistep strategy of biochemical surface modifications that resulted in the synthesis of new, effective and biocompatible intravascular implants coating with immobilized anti-CD133 antibodies, that proved to be the most effective in endothelial progenitor cells capture and reduced smooth muscle cells growth. Biomolecules were immobilized on differently functionalized surfaces. The distribution, nanostructural characteristics and intramolecular interactions of anti-CD133 molecules as well as their ability to bind EPCs was evaluated. We also tempted to build a molecular model of the CD133 protein to study antigen-antibody interactions. CD133 protein is expressed in endothelial progenitor cells (EPCs). Absence of preferential interaction site on CD133, but rather a presence of a small binding area, may be the specificity of reconnaissance sequence, thus importantly increasing the probability of CD133 protein binding. After all, regarding our molecular model, we are convinced that specific, and large enough interactions between anti-CD133 coating stent surface and CD133 present on EPCs will reduce risk of restenosis by favoring the endothelial growth. Additionally, the safety study of the vivo performance of modified titania based surface was performed using small animal models. No allergological or toxical local or systemic adverse effects of the developed coatings were noted.


Assuntos
Antígeno AC133/imunologia , Anticorpos Imobilizados/imunologia , Adesão Celular , Proliferação de Células , Células Progenitoras Endoteliais/fisiologia , Miócitos de Músculo Liso/citologia , Stents , Animais , Anticorpos Imobilizados/química , Anticorpos Monoclonais/imunologia , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Reestenose Coronária/prevenção & controle , Células Progenitoras Endoteliais/citologia , Feminino , Cobaias , Humanos , Masculino , Ratos , Ratos Wistar
11.
J Orthop Res ; 37(1): 35-50, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30370699

RESUMO

The biology of bone healing is a rapidly developing science. Advances in transgenic and gene-targeted mice have enabled tissue and cell-specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing-coupled with the heterogeneity of animal models-renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.


Assuntos
Consolidação da Fratura/imunologia , Osteogênese , Transdução de Sinais , Animais , Calo Ósseo/fisiologia , Condrócitos/fisiologia , Células Progenitoras Endoteliais/fisiologia , Humanos , Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica , Osteoblastos/fisiologia , Osteoclastos/fisiologia
12.
Theranostics ; 8(20): 5703-5712, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555575

RESUMO

Pre-vascularised cell sheets have been used to promote early angiogenesis and graft survival. However, the use of pre-vascularised mucosal cell sheets for burn wounds has been rarely evaluated. Therefore, we examined the applicability of an oral pre-vascularised mucosal cell sheet that we had previously developed for the treatment of cutaneous burn wounds. Methods: Mucosal keratinocytes, fibroblasts, and endothelial progenitor cells were isolated from the oral mucosa and peripheral blood and were expanded in vitro. Mucosal cell sheets were generated by seeding cultured keratinocytes onto a mixture of fibroblasts, endothelial cells, and fibrin. Third-degree burn wounds were created on the backs of rats and were covered with the cell sheets, skin grafts, or silastic sheets as a control. Gross and microscopic findings and gene expression profiles of wounds were compared among the groups. Results: CD31-positive microvessels were observed in the fibrin-matrix layer of the cell sheet. In the cutaneous burn wound model, the cell sheets promoted wound healing, with accelerated wound closure and less scarring than with silastic sheets and skin grafts. The cell sheets had more microvessels and proliferating cells and less neutrophil infiltration and fibrotic features than the controls or skin grafts. The cell sheet induced higher mRNA expression of KRT14, VEGFA, IL10, and AQP3 and lower mRNA expression of TGFB1, IL6, ICAM1, ACTA2, and FN1 than did the controls or skin grafts. Conclusions: The pre-vascularised mucosal cell sheet promotes cutaneous burn wound healing.


Assuntos
Queimaduras/terapia , Mucosa Bucal/fisiologia , Transplante de Pele/métodos , Engenharia Tecidual/métodos , Cicatrização , Animais , Células Sanguíneas/fisiologia , Queimaduras/patologia , Modelos Animais de Doenças , Células Progenitoras Endoteliais/fisiologia , Fibroblastos/fisiologia , Perfilação da Expressão Gênica , Histocitoquímica , Queratinócitos/fisiologia , Ratos , Resultado do Tratamento
13.
Eur J Med Res ; 23(1): 56, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413175

RESUMO

BACKGROUND: Both psoriasis (Ps) and psoriasis arthritis (PsA) have been associated with increased cardiovascular risk. Also, both are characterized by increased neovascularization. Endothelial progenitor cells (EPCs) have been implicated in promoting vascular repair in ischemic diseases. The aim of the study was to correlate the EPC system with CV risk factors and with parameters of vascular stiffness in Ps and PsA. METHODS: Twenty-six healthy subjects, 30 patients with Ps, and 31 patients PsA were included in the study. eEPC regeneration was evaluated by a colony-forming assay, circulating eEPCs were measured by cytometric analysis. For vascular analysis, all subjects underwent quantification of pulse wave velocity (PWV) and augmentation index (AIX). RESULTS: Patients were categorized upon the duration of disease, severity of skin involvement (PASI-Ps), individual pain as reflected by the VAS (PsA), CRP values, and history of treatment with one or more biologicals. Regarding the eEPC system, no significant differences were observed between the respective categories. Correlation analyses between parameters of vascular stiffness (PWV and AIX) and patterns of colony formation/circulating eEPCs did not show any correlation at all. CONCLUSION: Parameters of vascular stiffness are not significantly deteriorated in Ps/PsA. Thus, pulse wave analysis may not be suitable for CVR assessment in certain autoimmune-mediated diseases. Regenerative activity of the eEPC system/circulating eEPC numbers are not altered in Ps/PsA. One may conclude that malfunctions of the eEPC are not substantially involved in perpetuating the micro-/macrovascular alterations in Ps/PsA.


Assuntos
Artrite Psoriásica/fisiopatologia , Células Progenitoras Endoteliais/fisiologia , Psoríase/fisiopatologia , Rigidez Vascular/fisiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Medição de Risco , Fatores de Risco
14.
J Neurosurg ; 131(3): 884-891, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30485214

RESUMO

OBJECTIVE: The relationship between intraplaque hypoxia and intraplaque hemorrhage (IPH) has been reported, but the details remain obscure. In this study, the authors aimed to clarify the relationship among intraplaque hypoxia, endothelial progenitor cells (EPCs), and neovascularization, which causes IPH. The histological findings of specimens obtained from carotid endarterectomy were assessed. METHODS: This study included 49 patients who underwent carotid endarterectomy. Magnetic resonance plaque imaging was performed to analyze the components of the carotid plaques, and surgical specimens were subjected to immunohistochemical analysis. The numbers of hypoxia-inducible factor-1 alpha (HIF-1α)-, CD34-, CD133-, and vascular endothelial growth factor receptor-2 (VEGFR-2)-positive cells in the carotid plaques were precisely quantified, as were the number and maximum diameter of CD31-positive microvessels. RESULTS: Plaque components were judged as fibrous in 7 samples, lipid-rich in 22, and IPH in 20. The number of CD34-, VEGFR-2-, and CD133-positive cells as an EPC-specific marker was significantly correlated with the number of HIF-1α-positive cells (r = 0.9, r = 0.82, and r = 0.81, respectively). These numbers varied among the 3 plaque components (IPH > lipid-rich > fibrous). The number and maximum luminal diameter of CD31-positive microvessels were also significantly correlated with the number of HIF-1α-positive cells (r = 0.85 and r = 0.89, respectively) and varied among the 3 plaque components (IPH > lipid-rich > fibrous). CONCLUSIONS: The present findings suggest that intraplaque hypoxia may accelerate abnormal microvessel formation derived from EPCs, which in turn promotes IPH. The results also suggest that microvessel enlargement is a pivotal characteristic of IPH and these enlarged microvessels are immature endothelial tubes with disorganized branching and are fragile and prone to rupture.


Assuntos
Estenose das Carótidas/metabolismo , Células Progenitoras Endoteliais/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/complicações , Neovascularização Patológica/complicações , Placa Aterosclerótica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Estenose das Carótidas/etiologia , Estenose das Carótidas/patologia , Endarterectomia das Carótidas , Feminino , Humanos , Hipóxia/metabolismo , Masculino , Neovascularização Patológica/metabolismo , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/patologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
Med Sci Monit ; 24: 6187-6199, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30183690

RESUMO

BACKGROUND The therapeutic potential of endothelial colony-forming cells (ECFCs) may be impaired in an ischemic environment. Direct injection of ECFCs is not an effective method of rescuing the ischemic heart, but exosomes derived from these cells may be a promising therapeutic tool. However, exosomes produced under normoxia and hypoxia may not be identical. Therefore, the purpose of this study was to investigate alterations in the anti-fibrotic effects of hypoxia-treated ECFC-derived exosomes and the underlying mechanism involved. MATERIAL AND METHODS ECFCs were isolated from peripheral blood and exosomes were collected from ECFCs treated with normoxia (nor-exo) or hypoxia (hyp-exo). Effects of exosomes on cardiac fibroblast activation were evaluated in vitro. MicroRNAs (miRNAs) inside the exosomes were extracted and compared using next-generation RNA sequencing. Predicted target mRNAs of miR-10b-5p were validated using a dual-luciferase reporter gene assay method. RESULTS Nor-exo significantly ameliorated cardiac fibroblast activation in vitro. These effects were attenuated in the hyp-exo-treated group. miR-10b-5p was enriched in nor-exo but not in hyp-exo. Dual-luciferase reporter gene assay found that both SMAD-specific E3 ubiquitin protein ligase 1 (Smurf1) and histone deacetylase 4 (HDAC4) mRNAs were inhibited by miR-10b-5p. The expression of neutral sphingomyelinase 2 (N-SMase2) was decreased in hypoxia ECFCs, and this result was consistent with the changes in miR-10b-5p in hyp-exo. CONCLUSIONS Due to a reduction of miR-10b-5p, which targets the fibrotic genes Smurf1 and HDAC4, the anti-fibrotic effects of hyp-exo were abolished.


Assuntos
Exossomos/metabolismo , Fibrose/metabolismo , Hipóxia/metabolismo , Células Cultivadas , China , Células Endoteliais/metabolismo , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/fisiologia , Exossomos/genética , Exossomos/ultraestrutura , Fibrose/genética , Genes Reporter/genética , Células HEK293 , Sequenciamento de Nucleotídeos em Larga Escala , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , MicroRNAs/genética , RNA Mensageiro/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
16.
Clin Sci (Lond) ; 132(17): 1977-1994, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-30220651

RESUMO

Chronic kidney disease (CKD) is a major and growing public health concern with increasing incidence and prevalence worldwide. The therapeutic potential of stem cell therapy, including mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) holds great promise for treatment of CKD. However, there are significant bottlenecks in the clinical translation due to the reduced number of transplanted cells and the duration of their presence at the site of tissue damage. Bioengineered hydrogels may provide a route of cell delivery to enhance treatment efficacy and optimise the targeting effectiveness while minimising any loss of cell function. In this review, we highlight the advances in stem cell therapy targeting kidney disease and discuss the emerging role of hydrogel delivery systems to fully realise the potential of adult stem cells as a regenerative therapy for CKD in humans. MSCs and EPCs mediate kidney repair through distinct paracrine effects. As a delivery system, hydrogels can prolong these paracrine effects by improving retention at the site of injury and protecting the transplanted cells from the harsh inflammatory microenvironment. We also discuss the features of a hydrogel, which may be tuned to optimise the therapeutic potential of encapsulated stem cells, including cell-adhesive epitopes, material stiffness, nanotopography, modes of gelation and degradation and the inclusion of bioactive molecules. This review concludes with a discussion of the challenges to be met for the widespread clinical use of hydrogel delivery system of stem cell therapy for CKD.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Hidrogéis , Insuficiência Renal Crônica/terapia , Transplante de Células-Tronco/métodos , Células Progenitoras Endoteliais/fisiologia , Humanos , Células-Tronco Mesenquimais/fisiologia , Regeneração , Medicina Regenerativa/métodos , Medicina Regenerativa/tendências , Insuficiência Renal Crônica/fisiopatologia , Engenharia Tecidual/métodos , Engenharia Tecidual/tendências
17.
Stem Cells ; 36(12): 1863-1874, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30171660

RESUMO

Efficient recruitment and angiogenesis of endothelial progenitor cells (EPCs) are critical during a thrombus event. However, the details of EPC recruitment and the regulation of angiogenesis have not been fully determined. The aim of this study was to determine the role of the long noncoding (lnc)RNA Wilms tumor 1 associated protein pseudogene 1 (WTAPP1) in regulation of the migration and angiogenesis of EPCs. EPCs were isolated from human peripheral blood and characterized by flow cytometry, after which lentivirus-mediated lncRNA WTAPP1 overexpression and knockdown were performed. Scratch assay, Transwell assay, and in vitro and in vivo tube formation assays were performed to measure cell migration, invasion, and angiogenic abilities, respectively. Moreover, a microarray screen, bioinformatic prediction, and quantitative PCR and Western blot of miRNAs interacting with lncRNA WTAPP1 were conducted. Western blot was carried out to elucidate the relationship among WTAPP1, miR-3120-5P, and MMP-1 in the autophagy pathway. WTAPP1 positively regulated migration, invasion, and in vitro and in vivo tube formation in EPCs by increasing MMP-1 expression and activating PI3K/Akt/mTOR signaling. Furthermore, WTAPP1 contains a putative miR-3120-5P binding site. Suppression of WTAPP1 by miR-3120-5P decreased the level of MMP-1. In addition, we demonstrated that suppression of the autophagy pathway is involved in the effects of WTAPP1 on EPC migration and angiogenesis. The lncRNA WTAPP1, a molecular decoy for miR-3120-5p, regulates MMP-1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in EPCs. Acting as a potential therapeutic target, the lncRNA WTAPP1 may play an important role in the pathogenesis of DVT. Stem Cells 2018;36:1863-12.


Assuntos
Movimento Celular/fisiologia , Células Progenitoras Endoteliais/fisiologia , Metaloproteinase 1 da Matriz/metabolismo , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Autofagia , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Humanos , Masculino , Metaloproteinase 1 da Matriz/genética , Camundongos , Camundongos Nus , MicroRNAs/genética , Neovascularização Fisiológica/fisiologia , Transdução de Sinais
18.
Sci Rep ; 8(1): 14239, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30250055

RESUMO

Endothelial progenitor cell (EPC) transplantation is beneficial for ischemic diseases such as critical limb ischemia and ischemic heart disease. The scarcity of functional EPCs in adults is a limiting factor for EPC transplantation therapy. The quality and quantity culture (QQc) system is an effective ex vivo method for enhancing the number and angiogenic potential of EPCs. Further, microgravity environments have been shown to enhance the functional potential of stem cells. We therefore hypothesized that cells cultured with QQc under microgravity may have enhanced functionality. We cultured human peripheral blood mononuclear cells using QQc under normal (E), microgravity (MG), or microgravity followed by normal (ME) conditions and found that ME resulted in the most significant increase in CD34+ and double positive Dil-Ac-LDL-FITC-Ulex-Lectin cells, both EPC markers. Furthermore, angiogenic potential was determined by an EPC-colony forming assay. While numbers of primitive EPC-colony forming units (pEPC-CFU) did not change, numbers of definitive EPC-CFU colonies increased most under ME conditions. Gene-expression profiling also identified increases in angiogenic factors, including vascular endothelial growth factor, under MG and ME conditions. Thus, QQc along with ME conditions could be an efficient system for significantly enhancing the number and angiogenic potential of EPCs.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Neovascularização Fisiológica/genética , Ausência de Peso , Antígenos CD34/genética , Técnicas de Cultura de Células , Diferenciação Celular/genética , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Células Progenitoras Endoteliais/fisiologia , Células Progenitoras Endoteliais/efeitos da radiação , Sangue Fetal/efeitos da radiação , Expressão Gênica/genética , Expressão Gênica/efeitos da radiação , Humanos , Leucócitos Mononucleares/fisiologia , Leucócitos Mononucleares/efeitos da radiação , Neovascularização Fisiológica/fisiologia , Neovascularização Fisiológica/efeitos da radiação , Transplante de Células-Tronco/métodos , Células-Tronco/metabolismo
19.
Curr Res Transl Med ; 66(3): 71-82, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30108025

RESUMO

Patients with systemic lupus erythematosus (SLE) have a tremendously increased risk for cardiovascular disease (CVD), which could not be accounted in entirety by traditional Framingham risk factors. To study whether the accelerated atherosclerosis in SLE patients is mediated by type I interferon (IFN-I) through the regulation of endothelial progenitor cells (EPCs), we created a line of C57BL/6 mice with deficiency in both apolipoprotein E (ApoE-/-) and fas ligand (FasL-/-, gld.). As expected, the resultant gld. ApoE-/- mice exhibited both aggravated lupus-like disease and atherosclerosis under normal diet. Increased expression of IFN-I-stimulated genes (ISGs) was closely associated with depletion and dysfunction of EPCs, as well as with accelerated atherosclerotic lesion in gld. ApoE-/- mice. While only IFN-α instead of other interventions, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IRS423 and IRS661, impaired EPC function in vitro. Mechanistically, activation or inhibition of the TLR7/9 signaling could modulate EPC number and function in vivo. Decreased proliferation rate and increased apoptotic rate of EPCs induced by IFN-α might contribute to the results to a certain extent. Thus, our data suggest that excessive expression of IFN-I through the activation of TLR7/9 signaling may induce accelerated atherosclerosis in lupus through the depletion or dysfunction of EPCs, suggesting that targeting IFN-I might have potential therapeutic effects on both lupus disease and premature atherosclerosis in SLE patients.


Assuntos
Apolipoproteínas E/genética , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/fisiologia , Proteína Ligante Fas/genética , Interferon Tipo I/genética , Animais , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Modelos Animais de Doenças , Células Progenitoras Endoteliais/patologia , Proteína Ligante Fas/deficiência , Feminino , Interferon Tipo I/metabolismo , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Knockout para ApoE , Transdução de Sinais/genética
20.
Sci China Life Sci ; 61(10): 1178-1188, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30159681

RESUMO

The rapid endothelialization of tissue-engineered blood vessels (TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases. ß-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded ß-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells (RAVECs). Subsequently, we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded ß-cyclodextrin sulfate, and these vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded ß-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy (SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded ß-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Flavonoides/farmacologia , beta-Ciclodextrinas/farmacologia , Animais , Prótese Vascular , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/fisiologia , Flavonoides/química , Ratos Sprague-Dawley , Sulfatos/metabolismo , Engenharia Tecidual/métodos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo
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