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1.
ESMO Open ; 7(3): 100498, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35642988

RESUMEN

BACKGROUND: While side-effects and health-related quality of life (QoL) are routinely assessed in clinical trials, commonly used tools do not measure patients' ability to maintain normal daily activities. QoL can be severely affected directly by the disease, the treatment side-effects and by personal and societal misconceptions promoting avoidance from activities perceived as dangerous for cancer patients. We examined practices of actively treated patients with cancer. METHODS: A questionnaire was designed, assessing daily activities (11 items) and dietary limitations (7 items) distributed between October and December 2019 (before the coronavirus pandemic) among patients treated at the Oncology Division of Tel Aviv Sourasky Medical Center. RESULTS: The study population comprised 208 patients who participated in the survey. The majority reported at least one social-environmental avoidance or dietary limitation (136, 65% and 120, 57.7%, respectively), including abstaining from social contact, avoiding pets, public domains, traveling and maintaining dietary constraints. Adoption of these measures was not associated with clinical, demographic factors and treatment type. The major sources guiding restrictions came from advice of non-medical personnel (55.7%), the Internet (7.2%) and personal choice by the patients themselves (24%). CONCLUSIONS: Most cancer patients reported compromised daily activities, which are likely attributed to misbeliefs about disease and treatment, and have a deleterious impact on QoL, in its wider sense, namely, the ability to conduct a full and meaningful life. These findings call for the development and implementation of tools examining patients' real-life activity, beyond side-effects or health-related QoL (HRQoL). We propose this assessment as an integral part in the evaluation of new drugs and technologies and as an additional endpoint in pivotal clinical trials.


Asunto(s)
Neoplasias , Calidad de Vida , Actividades Cotidianas , Humanos , Encuestas y Cuestionarios
2.
J Clin Apher ; 33(3): 404-408, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29114919

RESUMEN

OBJECTIVE: Familial hypercholesterolemia (FH) is a genetic disease with very high levels of circulating low density lipoprotein cholesterol (LDL-C) levels that leads to accelerated atherosclerosis. Lipoprotein apheresis is an effective treatment option for patients with FH and results in reduced cardiovascular morbidity and mortality. Circulating progenitor cells (CPCs) are markers of overall vascular health and diminished levels have been associated with decreased reparative potential and worse outcomes. We assessed the short-term change in CPC levels following a single lipoprotein apheresis session in FH patients who are already on stable lipoprotein apheresis therapy. We hypothesized that in addition to a reduction in atherogenic lipids, the cardiovascular benefit from lipoprotein apheresis therapy is mediated by enhanced vascular reparative capacity through mobilization of CPCs. METHODS: Eight FH patients (1 homozygous and 7 heterozygous) on stable lipoprotein apheresis therapy for at least three months had CPCs measured at baseline (prior to apheresis) and two hours after apheresis. Results were compared with data from age-matched hyperlipidemic (HLP) patients on statin therapy and healthy volunteers. RESULTS: FH patients had higher baseline circulating levels of CD34+/CD133+ and CD34+/CD133+/CXCR4+ cells compared to HLP and healthy subjects. There was no significant change in CPCs after apheresis in FH patients. CONCLUSIONS: FH patients had higher CPC counts at baseline compared to age-matched HLP and healthy controls, suggesting activation of reparative mechanism in this high risk population. Larger studies are needed to better characterize differences in CPC counts between FH subjects and HLP patients over time.


Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Hiperlipoproteinemia Tipo II/sangre , Células Madre/citología , Adulto , Antígenos CD34/análisis , Estudios de Casos y Controles , Recuento de Células , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/terapia , Lipoproteínas/aislamiento & purificación , Persona de Mediana Edad
3.
Bone Marrow Transplant ; 52(9): 1304-1310, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28581472

RESUMEN

Chronic GvHD (cGvHD) is the leading cause of late non-relapse mortality (NRM) and morbidity after allogeneic hematopoietic stem cell transplant (AHSCT). We analyzed the late effects of a phase II trial testing the efficacy of intermediate dose rabbit anti-thymocyte globulin (Thymoglobulin Thymo) in combination with tacrolimus and sirolimus (TTS) in 47 patients (pts) for the prevention of acute and chronic GvHD after unrelated AHSCT. The median follow-up was 45.2 months. The cumulative incidence of NIH severe cGvHD at 48 months was 6.4% with no new occurrences past 6 months for the entire follow-up period. The overall cumulative incidence of cGvHD was 44.7%. Out of 20 pts who are alive and disease-free at the last follow-up, only 4 pts continue to need systemic immune suppression. We observed low late NRM with only 3 transplant-related deaths after 6 months post transplant. At 4 years of follow-up, the overall cumulative incidence of NRM and disease relapse was 27.7% and 30.0%, respectively. PFS and overall survival (OS) at 4 years were 42 and 47%. At long term follow-up, TTS was associated with low incidence of severe cGvHD and late NRM.


Asunto(s)
Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/uso terapéutico , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico , Adulto , Anciano , Suero Antilinfocítico/farmacología , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Inmunosupresores/farmacología , Incidencia , Masculino , Persona de Mediana Edad , Medición de Riesgo , Sirolimus/farmacología , Tasa de Supervivencia , Tacrolimus/farmacología , Adulto Joven
5.
Bone Marrow Transplant ; 51(8): 1113-20, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27042847

RESUMEN

Several studies have reported an association between CMV reactivation and a decreased incidence of relapse for AML after adult donor allogeneic hematopoietic cell transplantation (HCT). Limited data, however, are available on the impact of CMV reactivation on relapse after cord blood (CB) stem cell transplantation. The unique combination of higher incidence of CMV reactivation in the seropositive recipient and lower incidence of graft versus host disease (GvHD) in CB HCT permits a valuable design to analyze the impact of CMV reactivation. Data from 1684 patients transplanted with CB between 2003 and 2010 for AML and ALL were analyzed. The median time to CMV reactivation was 34 days (range: 2-287). CMV reactivation and positive CMV serology were associated with increased non-relapse mortality (NRM) among both AML and ALL CB recipients (reactivation, AML: relative risk (RR) 1.41 (1.07-1.85); ALL: 1.60 (1.14-2.23); Serology, AML: RR 1.39 (1.05-1.85), ALL: RR 1.61 (1.18-2.19)). For patients with ALL, but not those with AML, this yielded inferior overall survival (P<0.005). Risk of relapse was not influenced by CMV reactivation or positive CMV serostatus for either disease.


Asunto(s)
Citomegalovirus/fisiología , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Activación Viral , Adolescente , Adulto , Anciano , Niño , Preescolar , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/mortalidad , Femenino , Enfermedad Injerto contra Huésped , Humanos , Lactante , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
7.
Bone Marrow Transplant ; 51(3): 333-43, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26642333

RESUMEN

Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and have important roles in hematopoietic engraftment, GvHD and graft-versus-leukemia responses following allogeneic hematopoietic cell transplantation (HCT). In addition, pDCs mediate antiviral immunity, particularly as they are the body's primary cellular source of type I interferon. Given their pleiotropic roles, pDCs have emerged as cells that critically impact transplant outcomes, including overall survival. In this article, we will review the pre-clinical and clinical literature, supporting the crucial roles that pDCs assume as key immune effector cells during HCT.


Asunto(s)
Células Dendríticas/inmunología , Trasplante de Células Madre Hematopoyéticas , Inmunidad Celular , Inmunidad Innata , Células Plasmáticas/inmunología , Aloinjertos , Humanos , Virosis/etiología , Virosis/inmunología
10.
Bone Marrow Transplant ; 50(3): 432-7, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25599169

RESUMEN

Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10(6)/L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30⩽400 × 10(6)/L was associated with worse OS, increased NRM and severe aGVHD.


Asunto(s)
Enfermedad Injerto contra Huésped/sangre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfocitos/patología , Estudios de Cohortes , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo
11.
Bone Marrow Transplant ; 49(9): 1176-83, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24955785

RESUMEN

HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor (UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06-1.53; P=0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37-0.80; P=0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.


Asunto(s)
Epítopos de Linfocito T/inmunología , Cadenas alfa de HLA-DP/inmunología , Cadenas beta de HLA-DP/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Mapeo Epitopo , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Riesgo , Donante no Emparentado , Adulto Joven
12.
Leukemia ; 28(3): 658-65, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23989431

RESUMEN

The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.


Asunto(s)
Trasplante de Médula Ósea , Neoplasia Residual , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Inducción de Remisión , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Adulto , Animales , Femenino , Cobayas , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Trasplante Homólogo , Adulto Joven
13.
Radiat Prot Dosimetry ; 161(1-4): 257-60, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24162375

RESUMEN

Tissue-equivalent proportional counters (TEPC) can potentially be used as a portable and personal dosemeter in mixed neutron and gamma-ray fields, but what hinders this use is their typically large physical size. To formulate compact TEPC designs, the use of a Monte Carlo transport code is necessary to predict the performance of compact designs in these fields. To perform this modelling, three candidate codes were assessed: MCNPX 2.7.E, FLUKA 2011.2 and PHITS 2.24. In each code, benchmark simulations were performed involving the irradiation of a 5-in. TEPC with monoenergetic neutron fields and a 4-in. wall-less TEPC with monoenergetic gamma-ray fields. The frequency and dose mean lineal energies and dose distributions calculated from each code were compared with experimentally determined data. For the neutron benchmark simulations, PHITS produces data closest to the experimental values and for the gamma-ray benchmark simulations, FLUKA yields data closest to the experimentally determined quantities.


Asunto(s)
Protección Radiológica/instrumentación , Radiometría/instrumentación , Radiometría/métodos , Algoritmos , Simulación por Computador , Diseño de Equipo , Rayos gamma , Humanos , Cinética , Método de Montecarlo , Neutrones , Fantasmas de Imagen , Protección Radiológica/métodos , Programas Informáticos , Distribución Tisular
14.
Bone Marrow Transplant ; 49(2): 185-9, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24162613

RESUMEN

Reduced-intensity conditioning (RIC) permits allogeneic hematopoietic progenitor cell transplantation in patients who would not be considered candidates for transplantation using a myeloablative preparative regimen because of age, comorbidities or prior therapy. In the setting of myeloablative transplantation, use of antithymocyte globulin (ATG) can reduce the risk of GVHD without negatively affecting transplant outcomes; however, limited data exist on the impact of ATG in the setting of RIC, particularly when there is HLA-mismatch. We performed a retrospective analysis of 85 patients who received unrelated donor transplants at our institution for hematologic malignancies following conditioning with fludarabine and melphalan (FluMel), with or without rabbit ATG (6 mg/kg). ATG was targeted to patients receiving HLA-mismatched grafts. With a median follow-up of 36 months, those receiving ATG and a mismatched graft had similar rates of acute and chronic GVHD, relapse, and similar OS compared with those receiving HLA-matched grafts without ATG. In a multivariate analysis, HLA-mismatched donor was not associated with a decrement in OS. We conclude that this intermediate dose of ATG is effective in preventing severe GVHD in the setting of HLA-mismatch, without undue compromise of the graft versus tumor effects on which RIC transplants depend.


Asunto(s)
Enfermedad Injerto contra Huésped/prevención & control , Adulto , Anciano , Animales , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Conejos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodos , Resultado del Tratamiento , Donante no Emparentado , Adulto Joven
15.
J Psychosom Res ; 73(5): 375-82, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23062812

RESUMEN

OBJECTIVE: The purpose of this study was to examine the influence of attachment, social support and the quality of the current partnership on the outcome of bereavement after perinatal loss. METHODS: In a prospective cohort design 33 women after perinatal loss were approached on admission to hospital and reassessed four weeks, four months and nine months later. The initial assessment included the Adult Attachment Interview and self-report questionnaires for social support and quality of the current partnership. Bereavement outcome was assessed using measures of grief (MTS), depression and anxiety (HADS), psychological distress (BSI), somatisation (BSI-SOM) and symptoms of PTSD (PDS). RESULTS: All measures of outcome showed a significant improvement over time. Standardized effect sizes between the initial assessment and nine month follow-up ranged between .36 for anxiety (HADS) and 1.02 for grief (MTS). Social support, quality of the partnership and secure attachment correlated inversely, and insecure preoccupied attachment correlated positively with the outcome measures. Preoccupied attachment was included as a predictor in two multivariate statistical models of non-linear regression analysis, one with somatisation (adjusted R2=.698, P=.016), the other with posttraumatic stress symptoms at nine month follow-up (adjusted R2=.416, P=.002) as target variable. Initial assessment scores of psychological distress predicted the course of the respective measure during follow-up (adjusted R2=.432, P=.014). CONCLUSION: Attachment, social support and the quality of the current partnership have an impact on the course of bereavement after perinatal loss. Secondary prevention after the event may focus on these factors in order to offer specific counselling and support.


Asunto(s)
Aborto Espontáneo/psicología , Adaptación Psicológica , Aflicción , Apego a Objetos , Mortinato/psicología , Adolescente , Adulto , Ansiedad/psicología , Depresión/psicología , Femenino , Humanos , Individualidad , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Apoyo Social
16.
Bone Marrow Transplant ; 47(10): 1350-5, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22327131

RESUMEN

This prospective, randomized, double-blind, placebo-controlled study evaluated the efficacy of palifermin to reduce the incidence of severe (grade 3-4) acute GVHD after myeloablation and allo-SCT. Adults who received allo-SCT for hematologic malignancies received placebo or palifermin 60 µg/kg daily on three consecutive days before conditioning and a single dose of 180 µg/kg after conditioning, but often 1 or 2 days before allo-SCT. Subjects received MTX (plus CYA or tacrolimus) on days 1, 3, 6 and 11. Acute GVHD was evaluated once weekly and oral mucositis was evaluated daily. Subjects were randomly assigned to placebo (n=78) or palifermin (n=77). Conditioning included TBI in approximately half of the subjects (48% placebo, 51% palifermin). The primary efficacy end point, subject incidence of grade 3-4 acute GVHD, was similar between treatment groups (17% placebo, 16% palifermin). Grade 3-4 oral mucositis (73% placebo, 81% palifermin) and other secondary efficacy end points were similar between treatment groups. The most commonly reported treatment-related adverse events were skin/s.c. events such as rash, pruritus, and erythema. This exploratory study of acute GVHD after myeloablation and allo-SCT did not provide evidence of a treatment effect with this dosing regimen of palifermin.


Asunto(s)
Factor 7 de Crecimiento de Fibroblastos/administración & dosificación , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Trasplante de Células Madre , Estomatitis/tratamiento farmacológico , Acondicionamiento Pretrasplante , Enfermedad Aguda , Adolescente , Adulto , Método Doble Ciego , Femenino , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Trasplante Homólogo
17.
Psychol Health ; 27(10): 1150-65, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22260304

RESUMEN

Complex regional pain syndrome (CRPS) is difficult to diagnose and is characterised by burning pain in one or more limbs. Treatment is palliative not curative and focuses on improving function. This requires patients to make long-term changes to their behaviour. As with all such regimens, adherence is often poor. This study explored the lived experience of 10 patients who had returned home after completing a two-week in-patient treatment programme. The interviews focused on how they coped with the transition from hospital to home, and on the things that they considered had facilitated or hindered this transition. Battling for control was an overarching theme that connected the four superordinate themes: 'gaining momentum' that facilitated the implementation of treatment advice, 'distance from the pool of expertise' that detailed the barriers to adherence experienced; 'It helped me realise it was not all in my head' that detailed a facilitative process, and the 'nag list' that was a technique patients' used to garner support. This article offers insights into the transition experience. A key outcome is the recognition of the need to better prepare patients for their transition back home.


Asunto(s)
Síndromes de Dolor Regional Complejo/rehabilitación , Continuidad de la Atención al Paciente , Servicios de Atención de Salud a Domicilio , Adaptación Psicológica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Adulto Joven
18.
Am J Transplant ; 11(9): 1825-34, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21884408

RESUMEN

HLA-matched bone marrow transplantation (BMT) is a cure for nonmalignant hematological disorders; however, rejection rates are high and correlate with the number of antecedent transfusions. Recently, using murine models, we reported that minor antigens (mHAs) in transfused leukoreduced red blood cell (RBC) or platelet units induce rejection of subsequent BMT. To study RBCs as an immunogen, we utilized transgenic donors that express a model mHA selectively on RBCs (HOD mouse). Transfusion of HOD blood did not induce BMT rejection of marrow that shared mHAs with the HOD RBCs. Similarly, no endogenous anti-HOD CD8(+) T-cell response was detected with antigen-specific tetramer reagents. Adoptively transferred OT-I T cells rapidly expanded after HOD blood transfusion; however, only a semi-effector phenotype was observed (tumor necrosis factor-α and interferon-γ secretion, but essentially no Granzyme B). After initial expansion, OT-I T cells contracted rapidly to very low levels. A similar trend was observed by in vivo CTL assay, with only transient lytic activity. Together, these data indicate that RBCs may not be the component of RBC units that induces BMT rejection, and suggest that contaminating platelets or leukocytes may be responsible.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Transfusión de Eritrocitos , Eritrocitos/inmunología , Animales , Apoptosis , Citometría de Flujo , Rechazo de Injerto/inmunología , Ratones , Ratones Endogámicos C57BL
19.
Cell Transplant ; 20(9): 1431-43, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21294961

RESUMEN

Endothelial progenitor cells (EPCs) consist of two different subpopulations named early (eEPCs) and late EPCs (lEPCs) that are derived from CD14(+) and CD14(-) circulating cells, respectively. These cells are regularly cultured over fibronectin-coated surfaces in endothelial basal medium (EBM)-2 supplemented with insulin-like growth factor (IGF-1), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF). We have developed a new and simplified method for culturing human EPCs obtained from peripheral blood and tested their ability to preserve cardiac function following infarction. We first demonstrated that eEPCs derived from human peripheral blood mononuclear cells (PBMCs) and cultured in EBM-2 medium supplemented with autologous serum (10%) over fibronectin-coated surfaces (10 µg/ml) in the presence of IGF-1 (50 ng/ml) only, have a secretome similar to eEPCs cultured under regular conditions with IGF-1, VEGF, EGF, and FGF. Our data also indicate that IGF-1 modulates PBMC secretome in a dose-dependent manner. In another series of experiments, we showed that PBMCs cultured in suspension in bags (S-PBMCs) in basal medium supplemented with fibronectin and IGF-1 secrete significant amounts of stem cell factor (SCF, 31.3 ± 3.1 pg/ml)), hepatocyte growth factor (HGF, 438.6 ± 41.4 pg/ml), soluble tumor necrosis factor receptor 1 (sTNFR1, 127.1 ± 9.9 pg/ml), VEGF (139.3 ± 9.6 pg/ml), and IGF-1 (147.2 ± 46.1 pg/ml) but very low levels of TNF-α (13.4 ± 2.5 pg/ml). S-PBMCs injected intravenously into NOD SCID mice migrated to the injured myocardium, reduced cardiac fibrosis, enhanced angiogenesis, and preserved cardiac function after myocardial infarction (MI) in a manner similar to eEPCs cultured under standard conditions. In conclusion, we show in this study a refined and optimized method for culturing eEPCs. Our data indicate that S-PBMCs are composed of several cell populations including eEPCs and that they secrete high amounts of antiapoptotic, anti-inflammatory, and proangiogenic factors capable of preserving cardiac function following MI.


Asunto(s)
Células Sanguíneas/citología , Técnicas de Cultivo de Célula/métodos , Células Endoteliales/citología , Células Endoteliales/trasplante , Isquemia/terapia , Enfermedades Vasculares/terapia , Inductores de la Angiogénesis/metabolismo , Animales , Apoptosis/efectos de los fármacos , Células Sanguíneas/efectos de los fármacos , Células Sanguíneas/metabolismo , Adhesión Celular/efectos de los fármacos , Técnicas de Cultivo de Célula/economía , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Fibronectinas/farmacología , Pruebas de Función Cardíaca/efectos de los fármacos , Humanos , Mediadores de Inflamación/metabolismo , Inyecciones Intravenosas , Factor I del Crecimiento Similar a la Insulina/farmacología , Isquemia/complicaciones , Isquemia/fisiopatología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Infarto del Miocardio/complicaciones , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/terapia , Trasplante de Células Madre , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/fisiopatología
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