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1.
Pregnancy Hypertens ; 16: 42-47, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31056159

RESUMO

OBJECTIVE: The objective of our study was to determine levels of endothelial progenitor cells (EPCs) in preeclampsia and normotensive pregnant women. STUDY DESIGN: Prospective cohort study of women with preeclampsia and normotensive pregnancies. EPCs were estimated by flow cytometry. Multiple linear regression was used to assess the association of EPCs with preeclampsia adjusting for maternal age, body mass index (BMI), gestation and ethnicity. MAIN OUTCOME MEASURE: Levels of EPCs in preeclampsia and normotensive pregnancies, with CD-34 and vascular endothelial (VE)-cadherin as markers of EPCs. VE-cadherin is an endothelial cell adhesion molecule used to delineate endothelial lineage of EPCs. RESULTS: There were thirty women in the preeclampsia group and thirty-three in the normotensive group. The two groups were similar except for the BMI and blood pressures, which were higher in preeclampsia. On multiple linear regression, EPCs numbers were significantly higher by 29 (95% confidence interval 11.7-46.6, p = 0.001) in preeclampsia compared to the normotensive group. There was significant positive correlation between EPCs and systolic blood pressure in preeclampsia (Spearman correlation coefficient 0.39, p = 0.03). CONCLUSION: Although widely used in cardiovascular disease other than preeclampsia, this is the first study using VE-cadherin as a marker of endothelial lineage to define EPCs in preeclampsia. Our results suggest the higher number of EPCs in preeclampsia may be a response of the bone marrow to endothelial injury.


Assuntos
Antígenos CD34/sangue , Antígenos CD/sangue , Caderinas/sangue , Células Progenitoras Endoteliais/citologia , Pré-Eclâmpsia/diagnóstico , Diagnóstico Pré-Natal , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Modelos Lineares , Pré-Eclâmpsia/sangue , Gravidez , Estudos Prospectivos
2.
Nutr Metab Cardiovasc Dis ; 29(6): 604-610, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30952572

RESUMO

AIM: To evaluate the possible association between dietary habits and progenitor cells using data obtained from a randomized crossover trial using two different diets, lacto-ovo-vegetarian (VD) and Mediterranean (MD), the CARDIVEG study. METHODS AND RESULTS: Eighty clinically healthy subjects with a low-to-moderate cardiovascular risk profile (61 F; 19 M; mean age: 50.7 ± 11.6 years) were randomly assigned to isocaloric VD and MD diets lasting three months each, and then crossed. The two diets showed no effects on endothelial progenitor cells and circulating endothelial cells but opposite effects on circulating progenitor cells. In fact, VD determined significant (p < 0.05) and negative changes on circulating progenitor cells, with an average geometric variation of -130 cells/106 events for CD34+/CD45-/dim, -80 cells/106 events for CD133+/CD45-/dim, and -84 cells/106 events for CD34+/CD133+/CD45-/dim while MD determined significant (p < 0.05) and positive changes for CD34+/CD45-/dim levels, with a geometric mean increase of +54 cells/106 events. No significant correlations were observed between changes in progenitor cells and changes in inflammatory parameters during the VD phase. On the other hand, during the MD phase negative correlations between changes of CD34+/CD45-/dim and interleukin-6 (R = -0.324; p = 0.004) as well as interleukin-8 (R = -0.228; p = 0.04) and monocyte chemotactic protein-1 (R = -0.277; p = 0.01), were observed. These correlations remained significant also after adjustment for confounding factors only for CD34+/CD45-/dim and interleukin-6 (ß = -0.282; p = 0.018) and monocyte chemotactic protein-1 (ß = -0.254; p = 0.031). CONCLUSIONS: MD, but not VD, reported a significant and positive effect on circulating progenitor cells in a group of subjects at low-to-moderate cardiovascular risk, probably acting through the modulation of inflammatory parameters.


Assuntos
Antígenos CD/sangue , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Dieta Vegetariana , Mediadores da Inflamação/sangue , Prevenção Primária/métodos , Células-Tronco/metabolismo , Antígeno AC133/sangue , Adulto , Idoso , Antígenos CD34/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/imunologia , Quimiocina CCL2/sangue , Estudos Cross-Over , Feminino , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Antígenos Comuns de Leucócito/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
3.
Geriatr Gerontol Int ; 19(6): 557-562, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30920121

RESUMO

AIM: The cardio-ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34-positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34-positive cells. METHODS: We carried out a cross-sectional study of 249 Japanese men, aged 60-69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34-positive cells might indicate the influence of consumptive reduction of circulating CD34-positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34-positive cell levels, using the median value in this population (0.95 cells/µL) as the cut-off. RESULTS: For participants with low circulating CD34-positive cell levels, logarithmic values of circulating CD34-positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [ß] = -0.22, P = 0.014), but not for participants with high levels (ß = -0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima-media thickness were detected for participants with low circulating CD34-positive cell levels (ß = -0.02, P = 0.865), significant positive associations were identified for participants with high levels (ß = 0.22, P = 0.028). CONCLUSIONS: As circulating CD34-positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34-positive cell counts. Our results also show that a positive association between CAVI and carotid intima-media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis. Geriatr Gerontol Int 2019; 19: 557-562.


Assuntos
Tornozelo/irrigação sanguínea , Antígenos CD34/sangue , Endotélio Vascular/metabolismo , Idoso , Envelhecimento/sangue , Biomarcadores/sangue , Estudos Transversais , Endotélio Vascular/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Rigidez Vascular
4.
Transfus Apher Sci ; 58(2): 196-200, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30902449

RESUMO

INTRODUCTION: Umbilical cord blood units (UCBUs) are collected and cryopreserved in biobanks for a future transplant. Hematopoietic stem cells and hematopoietic progenitor cells (HSC/HPC) present in UCB can be damaged due to factors such as the cryopreservation process, the thawing process, and prolonged storage time. METHODS: UCBUs (n = 27) were obtained from the Biobank of the National Center of Blood Transfusion (NCBT) from Mexico. They contained three attached segments of UCBU, including 1.0-2.3 × 106 CD34+ cells prior to cryopreservation and were stored during the period from 2003 to 2015. Each UCB segment was thawed with three different methods and CD34 cells, CD45 cells, and 7-AAD were identified by flow cytometry. Furthermore, we carried out CFU assays, and trypan blue staining. RESULTS: Viable CD45+ (vCD45+) cells, vCD34+ cells, CFU, and percentage of E-Clone were not statistically significant among three different thawing methods. The number of vCD45+ and vCD34+ cells diminished in the three thawing methods compared with the same cells prior to their cryopreservation (p < 0.0001). vCD45+ and vCD34+ cells diminished in the ≥10-year cryopreservation group (p < 0.001). In addition, percentage of recovery of vCD45+ and vCD34+ cells diminished in this same group (p = 0.013 and p < 0.0001, respectively). CONCLUSION: The thawing methods did not affect either cell viability (vCD45+ and vCD34+ cells) or pluripotency (CFU, percentage of E-Clone) in attached segments of UCBUs. The ≥10-year cryopreservation time in attached segments of UCBUs alters the number of vCD45+ and vCD34+ cells; however, it does not affect their pluripotency.


Assuntos
Antígenos CD34/sangue , Sobrevivência Celular/fisiologia , Criopreservação/métodos , Sangue Fetal/química , Adulto , Feminino , Citometria de Fluxo , Humanos , Masculino , Adulto Jovem
5.
J Clin Apher ; 34(4): 407-415, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30829422

RESUMO

BACKGROUND AND OBJECTIVES: The number of CD34+ cells collected in apheresis procedures depends mainly on the collection efficiency of the device and the blood volume processed. Large volume leukapheresis (LVL) can improve CD34+ cell yield and has previously been investigated using the COBE Spectra device (Terumo BCT, USA). MATERIALS AND METHODS: This was a retrospective analysis of LVL performance in patients undergoing continuous mononuclear cell collection (CMNC) using the new Spectra Optia apheresis system (Terumo BCT, USA) at the University Hospital Center, Zagreb, from March 2016 to September 2016. CD34+ cell yield predictability, determined using a customized algorithm, was also assessed. RESULTS: In total, 67 procedures performed in 46 adults and 14 performed in 11 children were included in the analysis. In adults, 30 (65.2%) patients successfully reached their target preapheresis CD34+ cell count on day 1, with a median (interquartile range [IQR]) CD34+ collected cell dose of 4.8 × 106 /kg (2.3-10.6 × 106 /kg). In the pediatric group, 81.8% successfully collected the target CD34+ cell dose on the first day, with a median (IQR) CD34+ collected cell dose of 11.1 × 106 /kg (3.2-16.3 × 106 /kg). The customized algorithm showed a strong and significant linear correlation with actual CD34+ cell dose (P < 0.0001). CONCLUSION: The results of this study support the use of LVL and the customized prediction algorithm in apheresis procedures. The ability to tailor the procedure to meet the needs of the individual patient may help to minimize the blood volume processed, shorten the duration, reduce the volume of infused anticoagulants, and improve patient comfort.


Assuntos
Algoritmos , Antígenos CD34/sangue , Leucaférese/métodos , Células-Tronco de Sangue Periférico/citologia , Adulto , Criança , Feminino , Humanos , Leucaférese/instrumentação , Masculino , Medicina de Precisão , Estudos Retrospectivos , Resultado do Tratamento
6.
J Clin Apher ; 34(4): 373-380, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30694583

RESUMO

BACKGROUND: Poor mobilization results are unexpected after G-CSF-induced peripheral blood stem cell collection in healthy donors. However, 2%-5% of the donors are poor mobilizers. Factors predicting CD34+-cell yield after mobilization in related alternative donors are still poorly known. PATIENTS AND METHODS: Baseline characteristics and efficacy results of G-CSF induced mobilization of 159 adult healthy donors in our institution from 2008 to 2016 were retrospectively analyzed. All donors received 10 µg/kg of G-CSF once a day subcutaneously for 4 days. Leukapheresis started on the 5th day of G-CSF treatment. Donors were classified as poor mobilizers if they had less than 20 000 CD34 + cell/mL peripheral blood count in the 5th day of G-CSF treatment or if they needed three or more leukapheresis for graft collection. RESULTS: Age, weight, and platelet count before and after mobilization were significantly different between poor and good mobilizers. Poor mobilizers (n = 16) were older (50.6 vs 41.7 years, P = 0.002), weight lower (64 vs 75 kg, P = 0.00) and showed a lower platelet count before (199.5 vs 219.0 × 109 /L, P = 0.03) and after (192.5 vs 206 × 109 /L, P = 0.019) mobilization. In the multivariate analysis only the 30% of the variability of mobilization was explained by the model (sensitivity 80%, specificity 70%). CONCLUSION: In this cohort of healthy donors in a single institution, older age, less weight, and lower platelet count was associated with poorer mobilization. With clinical and analytic factors it is not possible to predict more than 30% of the variability. Further studies are needed to investigate new variables.


Assuntos
Antígenos CD34/sangue , Doadores de Sangue , Mobilização de Células-Tronco Hematopoéticas/normas , Células-Tronco de Sangue Periférico/citologia , Adulto , Fatores Etários , Idoso , Peso Corporal , Fator Estimulador de Colônias de Granulócitos/farmacologia , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos
7.
Hematology ; 24(1): 166-172, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30334700

RESUMO

OBJECTIVES: The diagnosis of myelodysplastic syndrome (MDS) is not always straightforward in the absence of objective markers such as ringed sideroblasts, an excess of blasts or clonal cytogenetic abnormalities. Moreover, the lack of specificity of morphological dysplasia makes the differentiation between MDS and other causes of peripheral cytopenia difficult. The WHO 2016 classification of MDS recognizes multiparameter flow cytometry (MFC) as an adjuvant tool for MDS diagnosis. An easily applicable MFC protocol based on CD34 and CD45 is proposed by Ogata et al. Furthermore, in the diagnostic workup of patients with peripheral cytopenia, the integration of MFC by means of a Lymphoid Screening Tube (LST) is recommended by the EuroFlow™ consortium. The aim of this study was to investigate whether the LST, supplemented with CD34, can be used to calculate the Ogata score, thereby obviating the need to run different flow cytometric tubes. METHODS: Bone marrow samples from 108 patients with peripheral cytopenia were analyzed (MDS n = 32; non-MDS n = 76). The LST used in the present study was based on the tube designed by the EuroFlow™ consortium, but with addition of CD34 and without TCRγδ. RESULTS: Rather low sensitivities of 55% in low-grade MDS patients and 80% in high-grade MDS patients were observed. However, a high specificity of 92% was found in the non-MDS group. CONCLUSION: Besides screening for clonal lymphocytes, plasma cells and blasts, an LST supplemented with CD34 allows the calculation of the Ogata score as an adjuvant tool in the diagnostic workup of cytopenic patients suspected of MDS.


Assuntos
Antígenos CD34/sangue , Medula Óssea/metabolismo , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Feminino , Humanos , Antígenos Comuns de Leucócito/sangue , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Plasmócitos/metabolismo , Plasmócitos/patologia
8.
J Clin Apher ; 34(1): 39-43, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30426567

RESUMO

BACKGROUND: Mobilization regimen choice is a significant contributing factor for successful hematopoietic progenitor cell (HPC) collection by leukocytapheresis and reaching the target CD34+ cell dose. How mobilization regimen affects collection efficiency and the quality of products collected using the Spectra Optia apheresis instrument is not fully known. METHODS: We evaluated the impact of granulocyte-colony stimulating factor (GCSF) and GCSF/plerixafor mobilization regimens on CE and product composition. We studied 373 leukocytapheresis HPC collections for 147 autologous transplants from January 1, 2010 to December 31, 2014. Patients were categorized in two groups; good mobilizers, mobilized with GCSF only (GM) and poor mobilizers, mobilized with GCSF and Plerixafor (PM). RESULTS: Overall, compared with PM group, total nucleated cell (TNC) yield was significantly lower in GM group (P = <.001). In contrast, median percent mononuclear cell (MNC) collected from GM (86.5%) was significantly higher than products collected from PM group (79.5%; P < .001). Compared with GM group, CD34+ cell CE was about 10% lower in PM group (P < .008). In addition, daily CD34+ cell/Kg yield was significantly higher in GM (2.08 × 10/Kg) compared with PM group (1.64 x 10/Kg, P = .019). Overall, the median number of collections per patient was two for GM and three for PM (P = .004). CONCLUSION: Products collected from PM group contained higher TNC content relative to GM group but had lower MNC enrichment, CD34+ cell CE and daily CD34+ cell yield per Kg.


Assuntos
Antígenos CD34/sangue , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Controle de Qualidade , Adulto , Autoenxertos , Contagem de Células , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Granulócitos/citologia , Compostos Heterocíclicos/uso terapêutico , Humanos , Leucaférese , Leucócitos Mononucleares/citologia , Masculino , Pessoa de Meia-Idade
9.
Transfusion ; 59(2): 681-685, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30537299

RESUMO

BACKGROUND: Umbilical cord blood (UCB) has become an important source of transplantable CD34+ hematopoietic progenitor cells. Cord blood banks (CBBs) can increase their efficiency by minimizing the processing of UCB units with low CD34+ content, which have a lower likelihood of transplant utilization. We sought to identify a readily available preprocessing metric that would correlate with CD34+ cell counts, without the cost of additional analysis. STUDY DESIGN AND METHODS: Data were compiled for 131 UCB units processed at the regional CBB. Preprocessing hematologic metrics, including complete blood count and differential, were compared to postprocessing CD34+ cell quantities. The data were divided into six groups of varying preprocessing metrics, then compared for significant differences in postprocessing CD34+ cell quantities to develop a screening guidance. RESULTS: UCB units with nucleated RBC (nRBC) content of 15% or greater were found to have a significant increase in CD34+ cell percentage (p < 0.00001) and total CD34+ cell content (p < 0.0001). Units with preprocessing total nucleated cell count (TNC) of ≥ 1.50 × 109 with nRBC content of 15% or greater, and for TNC ≥ of 2.00 × 109 with nRBC content less than15%, had a significant increase in CD34+ content (p < 0.05 and p < 0.001, respectively). Applied as a screening guideline, these units had an increase in mean CD34+ content from 6.24 × 106 to 9.27 × 106 . Units originally in the bottom and top quartiles of CD34+ content constitute 5% and 53% of processed units meeting these TNC/nRBC criteria, respectively. CONCLUSION: These screening criteria utilizing nRBC provides a guideline that public CBBs may use to increase their efficiency by minimizing the processing of UCB units with lower CD34+ cell content.


Assuntos
Antígenos CD34/sangue , Bancos de Sangue , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/citologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Contagem de Eritrócitos , Sangue Fetal/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Humanos , Contagem de Leucócitos
10.
Transfusion ; 59(2): 671-680, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30593675

RESUMO

BACKGROUND: Processed blood volume (PBV) required to obtain a predefined number of stem cells can be estimated from peripheral blood CD34+ cell concentration, body weight, and collection efficiency (CE). Because CE is indefinite, this study was designed to formulate and validate a new model of PBV based on stochastic CE distribution. STUDY DESIGN AND METHODS: Data were retrospectively collected on 146 peripheral blood stem cell harvests from 114 patients and donors in a single institution from April 2014 to February 2018. The training set consisted of all procedures performed from April 2014 to June 2016 and the validation set of all procedures performed from July 2016 to February 2018. A new algorithm, based on CE2 distribution of the training set, was affirmed using the validation set. The positive predictive value of the model was estimated from the expected percentage of procedures that reached the target CD34-positive dose, with predicted PBV processed as the gold standard. RESULTS: The 10th and 50th percentiles of CE2 were 33.4% and 52.5%, respectively. When PBV was assorted into three categories, defined as greater than 90%, 50% to 90%, and less than 50% of procedures reaching the targeted CD34-positive dose, the positive predictive values of the new model were 100%, 70%, and 100%, respectively. CONCLUSION: The new model was validated with a high positive predictive value and can reliably estimate the required PBV and the success rate corresponding to the PBV. The model can be utilized easily with a Web-based tool.


Assuntos
Antígenos CD34/sangue , Volume Sanguíneo , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Modelos Biológicos , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucaférese , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Processos Estocásticos , Transplante Autólogo
12.
Saudi J Kidney Dis Transpl ; 29(4): 785-792, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30152413

RESUMO

Endothelial progenitor cells (EPCs) CD34 are bone marrow-derived cells that decrease in chronic kidney disease (CKD) patients especially when they reach end-stage renal disease and may be a risk marker of cardiovascular (CV) diseases. The aim of our study is to investigate the endothelial progenitor cell CD 34 numbers in children with CKD on regular hemodialysis (HD) and detect their association with vascular stiffness. We recruited 25 children on regular HD, who were selected from the HD unit of Al-Zahraa Hospital, Al-Azhar University. Another group of 25 age and sex matched healthy children served as as controls. We investigated the number of EPC number (CD34) using flow cytometry, intima-media thickness (IMT), and the peak systolic velocity (PSV) of the main arteries including the (aorta, carotid, and femoral) arteries using Doppler ultrasound, this is in the same line with the routine and traditional investigations of the CV risk in the study groups. Children on regular HD have significantly lower EPC numbers (CD34 numbers) compared to their controls, the median and the inter equatorial range of CD34 was 57 (17-122) and five (3-6), respectively (P 0.001). Significant positive correlations were found between CD 34 and triglycerides serum level (r = 0.817, P = 0.001), also between CD34 with IMT and PSV of the aorta (r = 0.685, P = 0.000: r = 0.457, P = 0.022), respectively. CD34 is 88% sensitive and specific for the detection of CV risk in children on regular HD. EPC CD34 exhibited a higher predictive value for CV risk in children on regular HD. Reduced EPC numbers contribute to accelerated atherosclerosis.


Assuntos
Antígenos CD34/sangue , Doenças Cardiovasculares/epidemiologia , Células Progenitoras Endoteliais/citologia , Diálise Renal , Insuficiência Renal Crônica , Adolescente , Biomarcadores , Doenças Cardiovasculares/sangue , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Criança , Células Progenitoras Endoteliais/química , Feminino , Citometria de Fluxo , Humanos , Masculino , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Fatores de Risco , Triglicerídeos/sangue
13.
Leuk Res ; 72: 12-19, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30059823

RESUMO

A seven-color panel was used to detect minimal residual disease (MRD) in T cell acute lymphoblastic leukemia (T-ALL) via flow cytometry (FCM). Its availability and clinical significance were studied in T-ALL patients with newly diagnosed (n = 64), relapsed (n = 48) and morphologically complete remission (n = 103). The following four features were used to identify immature cCD3+ T cells: CD34+, TdT+, but mCD3-/dim+, and CD45dim+. Among these features, either TdT or CD34 expression was the most useful and were found in 93.8% of patients at diagnosis and 86.7% of patients who relapsed. Although some of the immature markers had disappeared in 23 of 59 cases after therapy, only one case presented with a false negative MRD. Of the 74 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), MRD-positive patients showed a higher relapse rate, a higher cumulative incidence of relapse at 4 years and a shorter median relapse-free survival than MRD-negative patients at post-HSCT(72.7% vs 17.3%, P = 0.000; 100% vs 19.9%, P < 0.0001; and 16 months vs undefined, P < 0.0001). We demonstrated that this panel could be applied to>97% of T-ALL patients to detect MRD and predict relapse after allo-HSCT even in the absence of the initial immunophenotype.


Assuntos
Antígenos CD34/sangue , DNA Nucleotidilexotransferase/sangue , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Proteínas de Neoplasias/sangue , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Indução de Remissão , Taxa de Sobrevida
14.
Heart Vessels ; 33(12): 1559-1569, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30003322

RESUMO

Bone marrow-derived endothelial progenitor cells (EPC) are released into the peripheral blood in situations of vascular repair/angiogenesis. Regulation of vascular repair and angiogenesis by EPC depends not only on the number of circulating EPC but also on their functionality. As endothelial cells can act as antigen-presenting cells in coronary artery disease (CAD), we postulated that EPC can be immune activated here as well. CD34+-EPC were isolated from peripheral blood of patients with ST-elevation myocardial infarction (STEMI, n = 12), non-STEMI/unstable angina (UA, n = 15), and stable CAD (SA, n = 18). Expression of HLA-DR, adhesion and costimulatory molecules by isolated CD34+-EPC were compared with levels in healthy controls (n = 18). There were no significant differences in VCAM-1 and CD80 expression by peripheral circulating CD34+-EPC between the four groups, yet expression of CD86 was highest in UA (p < 0.05). ICAM-1 expression was lowest in SA (p < 0.01). CD34+-EPC constitutively expressed HLA-DR across all groups. Of note, patients pretreated with HMG-CoA reductase inhibitors exhibited lower expression of VCAM-1 by CD34+-EPC throughout all patient groups; furthermore, statins significantly limited ex vivo-induced upregulation of ICAM-1 by TNF-alpha. To the best of our knowledge, this is the first study to examine the expression of immune markers in peripheral circulating CD34+-EPC ex vivo. We demonstrate that CD34+-EPC display different patterns of adhesion and costimulatory molecules in various states of CAD. Expression levels were affected by pretreatment with statins. Hence, immune activity of peripheral circulating CD34+ cells might play a pathophysiologic role in evolution of CAD.


Assuntos
Síndrome Coronariana Aguda/imunologia , Antígenos CD34/sangue , Células Endoteliais/imunologia , Imunidade Celular , Síndrome Coronariana Aguda/sangue , Adulto , Idoso , Biomarcadores/sangue , Contagem de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Stem Cell Rev Rep ; 14(5): 694-701, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29931411

RESUMO

BACKGROUND/OBJECTIVES: Sickle cell disease (SCD) complications mostly result from vascular dysfunction, concerning systemic microvasculature and cerebral large vessels. The aim of this cohort study was to identify potential circulating biomarkers predictive for further vascular event occurrence in pediatric SCD. METHODS: We consecutively enrolled 108 children with SCD at steady state, aged 3-18 years old (median 9.8 years). Hematology, coagulation, hemolysis, endothelial, platelet and vascular activation parameters were recorded at inclusion. Neurovascular and systemic vascular events were prospectively recorded during a mean follow-up period of 27 months. RESULTS: Patients at steady state displayed significantly higher hemolysis and platelet activation markers, higher leukocyte, CD34+ hematopoietic stem cell and microvesicle counts, and a pro-coagulant profile compared to controls matched for age and ethnicity. Circulating endothelial cell or nucleosome level did not differ. During the follow-up period, 36 patients had at least one neurovascular (n = 12) or systemic vascular event (n = 25). In a multivariate model, high CD34+ cell count was the best predictor for the occurrence of a vascular event (OR 1.2 for 1000 cell/mL increase, 95% CI [1.049-1.4], p = 0.013, sensitivity 53%, specificity 84% for a threshold of 8675 cells/mL). CONCLUSION: CD34+ cell count at steady state is a promising biomarker of further vascular event in children with SCD.


Assuntos
Anemia Falciforme/sangue , Antígenos CD34/sangue , Vasos Sanguíneos/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Adolescente , Anemia Falciforme/patologia , Biomarcadores/sangue , Plaquetas/metabolismo , Vasos Sanguíneos/patologia , Micropartículas Derivadas de Células/genética , Cerebelo/irrigação sanguínea , Criança , Pré-Escolar , Feminino , Células-Tronco Hematopoéticas/patologia , Humanos , Masculino
16.
Environ Health Prev Med ; 23(1): 16, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29724162

RESUMO

BACKGROUND: Hepatocyte growth factor (HGF) may act as a possible biochemical index for vascular damage, although evidence for the association between HGF and carotid intima-media thickness (CIMT) is limited. Since both HGF and circulating CD34-positive cells play an important role in endothelial repair, circulating CD34-positive cell levels may influence the association between HGF and CIMT. METHODS: We conducted a cross-sectional study of 269 elderly Japanese men aged 60-69 years who had undertaken an annual medical checkup from 2014 to 2015. RESULTS: The median value for circulating CD34-positive cells was 0.93 cells/µL. Among the study population, 135 men showed low circulating CD34-positive cell levels (≤ 0.93 cells/µL). By multivariable linear regression analysis, HGF was found to be significantly positively associated with CIMT only to participants with low circulating CD34-positive cell levels, with a multi-adjusted ß of 0.26 (p = 0.005) and 0.002 (0.986) for low and high circulating CD34-positive cell levels, respectively. In addition, a significant interaction was observed between HGF and circulating CD34-positive cell levels (low and high) on CIMT (multivariable p value of 0.049). A positive association exists between HGF and CIMT in elderly Japanese men, limited to participants with low circulating CD34-positive cell levels. CONCLUSION: A positive association exists between HGF and CIMT in community-dwelling elderly Japanese men, which is limited to participants with low numbers of circulating CD34-positive cells. Our findings indicate that circulating CD34-positive cell levels could determine the influence of HGF on CIMT in elderly Japanese men.


Assuntos
Antígenos CD34/sangue , Espessura Intima-Media Carotídea , Fator de Crescimento de Hepatócito/metabolismo , Idoso , Biomarcadores/sangue , Estudos Transversais , Humanos , Japão , Masculino , Pessoa de Meia-Idade
17.
Cardiovasc Diabetol ; 17(1): 65, 2018 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-29724198

RESUMO

AIMS: Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease. CD34+ endothelial Progenitor Cells (EPCs) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker. This study investigated whether the addition of saxagliptin, a DPP-IV inhibitor, to metformin, may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients. METHODS: In 12 week, double-blind, randomized placebo-controlled trial, 42 subjects already taking metformin 1-2 grams/day were randomized to placebo or saxagliptin 5 mg. Subjects aged 40-70 years with diabetes for < 10 years, with no known cardiovascular disease, BMI 25-39.9, HbA1C 6-9% were included. We evaluated EPCs number, function, surface markers and gene expression, in addition to arterial stiffness, blood biochemistries, resting energy expenditure, and body composition parameters. A mixed model regression to examine saxagliptin vs placebo, accounting for within-subject autocorrelation, was done with SAS (p < 0.05). RESULTS: Although there was no significant increase in CD34+ cell number, CD31+ cells percentage increased. Saxagliptin increased migration (in response to SDF1α) with a trend of higher colony formation count. MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells, indicating a functional improvement. Gene expression analysis showed an upregulation in CD34+ cells for antioxidant SOD1 (p < 0.05) and a downregulation in CD34- cells for IL-6 (p < 0.01). For arterial stiffness, both augmentation index and systolic blood pressure measures went down in saxagliptin subjects (p < 0.05). CONCLUSION: Saxagliptin, in combination with metformin, can help improve endothelial dysfunction in early diabetes before macrovascular complications appear. Trial registration Trial is registered under clinicaltrials.gov, NCT02024477.


Assuntos
Adamantano/análogos & derivados , Antígenos CD34/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptídeos/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Células Progenitoras Endoteliais/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Adamantano/administração & dosagem , Adamantano/efeitos adversos , Adulto , Idoso , Pressão Arterial/efeitos dos fármacos , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Dipeptídeos/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , District of Columbia , Método Duplo-Cego , Sinergismo Farmacológico , Quimioterapia Combinada , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos
18.
Microvasc Res ; 119: 1-6, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29604296

RESUMO

BACKGROUND: KLOTHO is a regulator of endothelial cells activity and integrity. It has been described for the first time because of its anti-aging properties. KLOTHO encoding gene is present in many functional variants in humans, including "KL-VS" variant that has been connected with longevity and cardiovascular disease development. Few mechanisms have been proposed to explain these associations, but none of them focused on cells from CD34+ population. The aim of our study was to investigate influence of KLOTHO KL-VS polymorphism on populations of CD34+ and CD34+VEGFR2+ cells. METHODS AND RESULTS: We examined 167 Polish subjects from Pomeranian region. The analysis concerned KL-VS polymorphism, flow cytometry evaluation of whole blood cells and determination of endothelium-associated serum/plasma factors. Our results indicate that individuals possessing at least one KL-VS allele are characterized by greater number of CD34+ and CD34+VEGFR2+ and their various subpopulations (CD34+CD133+, CD34+c-Kit+, CD34+CXCR4+ and CD34+VEGFR2+c-Kit+) than wild-type volunteers. This group also exhibited more favorable lipid profile and statistically insignificant decrease of vWF and angiotensin II in their blood, whereas VEGF levels were elevated. CONCLUSION: One of the mechanisms that are responsible for previously described KL-VS heterozygote advantage may be connected with maintaining greater size of hematopoietic and endothelial progenitor cells population.


Assuntos
Antígenos CD34/sangue , Células Progenitoras Endoteliais/metabolismo , Proteínas de Membrana/genética , Polimorfismo Genético , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Idoso , Biomarcadores/sangue , Contagem de Células , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polônia
19.
Atherosclerosis ; 271: 214-222, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29524864

RESUMO

BACKGROUND AND AIMS: Cardiovascular (CV) morbidity is increased in inflammatory joint diseases (IJD), as rheumatoid (RA) and psoriatic arthritis (PsA). Whereas increased prevalence of subclinical atherosclerosis has been reported in these conditions, whether an early myocardial functionality is also impaired remains unknown. The aim of this study was to evaluate the myocardial functionality by speckle-tracking echocardiography (STE) in recent onset RA and PsA patients and its potential associations with the levels of circulating CD34 + cells, vitamin D, and with disease activity. METHODS: STE was used to assess the myocardial functionality in patients with very early RA (n = 41) and PsA (n = 35) without traditional CV risk factors, and 58 matched healthy controls (HC). Global longitudinal and circumferential strain (GLS and GCS) was estimated. Pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) were measured as surrogate markers of atherosclerosis. Circulating CD34 + counts were evaluated by flow cytometry and vitamin D levels were quantified by HPLC. Disease activity was assessed by Disease Activity Score-28 (DAS28). RESULTS: RA patients exhibited impaired GLS and GCS (both p < 0.001) as compared to HC, GLS being also altered in PsA (p = 0.020 vs. HC). DAS28 was correlated to GLS (r = 0.908, p < 0.001) and GCS (r = 0.868, p < 0.001) in RA, these findings being confirmed by multivariate regression analyses adjusted for confounders and Principal Component Analyses. GLS and GCS were impaired in PsA patients with high disease activity as compared to HC, and GLS was found to be a predictor of cIMT in this condition. On the other hand, vitamin D was negatively associated with cIMT in HC (r = -0.308, p = 0.026) but not in PsA or RA, although decreased levels were observed (both p < 0.001). Vitamin D was an independent predictor of decreased CD34 + levels in PsA and RA. CD34 + counts negatively correlated DAS28, GLS and GCS in RA. CONCLUSIONS: Subclinical myocardial dysfunction is observed in IJD patients with preserved left-ventricular function and without traditional CV risk factors. Subclinical myocardial dysfunction was found to be a very early event in IJD. Disease activity was the main predictor of myocardial strain impairment. Interestingly, myocardial function was altered and associated with cIMT also in PsA patients with high disease activity.


Assuntos
Antígenos CD34/sangue , Artrite Psoriásica/epidemiologia , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Mediadores da Inflamação/sangue , Contração Miocárdica , Função Ventricular Esquerda , Vitamina D/sangue , Adulto , Idoso , Artrite Psoriásica/diagnóstico , Artrite Reumatoide/diagnóstico , Doenças Assintomáticas , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Espessura Intima-Media Carotídea , Diagnóstico Precoce , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia , Fatores de Tempo , Adulto Jovem
20.
Transfusion ; 58(6): 1452-1457, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29516519

RESUMO

BACKGROUND: Cord blood units (CBUs) are processed, frozen, and thawed before use in hematopoietic stem cell (HSC) transplantation. The manipulations affect HSC functionality, that is, induce apoptosis and reduce viability. HSC content, commonly expressed as CBU potency, that is, the expected ability of a CBU to restore hematopoiesis, is traditionally approximated through viable CD34+ cells and the colony-forming unit (CFU) cell cultivation assay. Alternative approaches, for example, the aldehyde dehydrogenase (ALDH) enzyme-based assay, are also forthcoming. We hypothesized that the ALDH assay might exclude apoptotic cells since it is based on enzyme activity. To investigate this, we designed a protocol for simultaneous staining of viable and apoptotic CD34+ and ALDH+ cells using 7-aminoactinomycin (7-AAD) and annexin V, in frozen-thawed CBUs. Results were correlated with results from the colony-forming unit-granulocyte/macrophage (CFU-GM) assay. STUDY DESIGN AND METHODS: Samples from 57 CBUs were thawed and simultaneously analyzed for CD34+ cells, ALDH+ cells, viability (7-AAD), and apoptosis (annexin V) using flow cytometry. Enumeration of CFUs was also performed. RESULTS: No nonviable and few apoptotic cells (mean 0.7%) were identified in the ALDH+ population compared to the viable CD34+ population (mean 3.6%). The total number of ALDH+ cells correlated better than viable CD34+ cells (r = 0. 72 vs. r = 0.66; p < 0.0001) with the results of the CFU assay. CONCLUSION: The ALDH assay excludes nonviable and apoptotic cells, and therefore correlates better with CFU enumeration compared to the number of viable CD34+ cells. We propose that the ALDH assay might replace the CFU-GM method in CBU potency measurements.


Assuntos
Aldeído Desidrogenase/metabolismo , Apoptose , Protocolos Clínicos/normas , Sangue Fetal/citologia , Antígenos CD34/sangue , Bancos de Sangue/métodos , Sobrevivência Celular , Ensaio de Unidades Formadoras de Colônias , Ensaios Enzimáticos/métodos , Ensaios Enzimáticos/normas , Sangue Fetal/enzimologia , Humanos
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