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1.
Rev Esc Enferm USP ; 55: e20200270, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34477195

RESUMO

OBJECTIVE: To assess the domains of quality of life related to hematologic cancer patient health in the first three years from autologous and allogeneic hematopoietic stem cell transplantation. METHOD: A prospective cohort from September 2013 to February 2019 at a reference service in Latin America with 55 patients. The instruments Quality of Life Questionnaire Core C30 and Functional Assessment Cancer Therapy - Bone Marrow Transplantation were used. For data analysis, Generalized Linear Mixed Model was used. RESULTS: The domains global and overall quality of life presented the lowest scores in the pancytopenia phase: 59.3 and 91.4 in autologous, 55.3 and 90.3 in allogeneic. The mixed method analysis has shown that there was a significant change in scores between the phases throughout the treatment (p< 0.05). CONCLUSION: Health-related quality of life presented significant changes in the domains between the phases throughout time. Understanding these results enables nursing interventions directed at the domains which were damaged during treatment.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transplante de Medula Óssea , Humanos , Estudos Prospectivos , Qualidade de Vida
2.
Saudi Med J ; 42(8): 847-852, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34344808

RESUMO

OBJECTIVES: To assess local epidemiology and risk factors for bacterial, fungal, and viral infections among the autologous bone marrow transplant population. METHODS: This study is a retrospective correlational cohort design comprising 150 adult patients who underwent autologous transplants at Princess Noorah Oncology Center, Jeddah, Saudi Arabia between 2014 and 2020. RESULTS: The study findings indicate that bacterial infection prevalence differed significantly across the different disease status pre-salvage as patients with the relapsed disease were more likely to have bacterial infections. The median of engraftment days differed significantly between those who had a bacterial infection and those who did not. Interestingly, previous pneumonia infection had a positive relationship with the number of hospital stays. CONCLUSIONS: Bacterial infections are the dominant type of infection among the autologous patient population. The research reflects authentic practice and reports unique characteristics of autologous transplant patients in terms of the prevalence and types of infection these patients experience.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Viroses , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Transplante Autólogo
3.
Molecules ; 26(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299512

RESUMO

Systemic steroids are used to treat acute graft-versus-host disease (aGVHD) caused by allogenic bone marrow transplantation (allo-BMT); however, their prolonged use results in complications. Hence, new agents for treating aGVHD are required. Recently, a new compound A (CpdA), with anti-inflammatory activity and reduced side effects compared to steroids, has been identified. Here, we aimed to determine whether CpdA can improve the outcome of aGVHD when administered after transplantation in a mouse model (C57BL/6 in B6D2F1). After conditioning with 9Gy total body irradiation, mice were infused with bone marrow (BM) cells and splenocytes from either syngeneic (B6D2F1) or allogeneic (C57BL/6) donors. The animals were subsequently treated (3 days/week) with 7.5 mg/kg CpdA from day +15 to day +28; the controls received 0.9% NaCl. Thereafter, the incidence and severity of aGVHD in aGVHD target organs were analyzed. Survival and clinical scores did not differ significantly; however, CpdA-treated animals showed high cell infiltration in the target organs. In bulk mixed lymphocyte reactions, CpdA treatment reduced the cell proliferation and expression of inflammatory cytokines and chemokines compared to controls, whereas levels of TNF, IL-23, chemokines, and chemokine receptors increased. CpdA significantly reduced proliferation in vitro but increased T cell infiltration in target organs.


Assuntos
Anti-Inflamatórios/farmacologia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Aguda , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Transplante de Medula Óssea/métodos , Proliferação de Células/efeitos dos fármacos , Quimiocinas/metabolismo , Modelos Animais de Doenças , Feminino , Doença Enxerto-Hospedeiro/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/efeitos dos fármacos
4.
Blood ; 138(3): 209-211, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34292329
5.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205205

RESUMO

Total body irradiation is a standard procedure of bone marrow transplantation (BMT) which causes a rapid increase in reactive oxygen species (ROS) in the bone marrow microenvironment during BMT. The increase in ROS reduces the engraftment ability of donor cells, thereby affecting the bone marrow recovery of recipients after BMT. In the early weeks following transplantation, recipients are at high risk of severe infection due to weakened hematopoiesis. Thus, it is imperative to improve engraftment capacity and accelerate bone marrow recovery in BMT recipients. In this study, we constructed recombinant copper/zinc superoxide dismutase 1 (SOD1) fused with the cell-penetrating peptide (CPP), the trans-activator of transcription (Tat), and showed that this fusion protein has penetrating ability and antioxidant activity in both RAW264.7 cells and bone marrow cells in vitro. Furthermore, irradiated mice transplanted with SOD1-Tat-treated total bone marrow donor cells showed an increase in total bone marrow engraftment capacity two weeks after transplantation. This study explored an innovative method for enhancing engraftment efficiency and highlights the potential of CPP-SOD1 in ROS manipulation during BMT.


Assuntos
Antioxidantes/farmacologia , Células da Medula Óssea/citologia , Peptídeos Penetradores de Células/genética , Produtos do Gene tat/genética , Proteínas Recombinantes de Fusão/farmacologia , Superóxido Dismutase-1/genética , Animais , Antioxidantes/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Transplante de Medula Óssea , Peptídeos Penetradores de Células/metabolismo , Células Cultivadas , Produtos do Gene tat/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio , Proteínas Recombinantes de Fusão/metabolismo , Superóxido Dismutase-1/metabolismo , Irradiação Corporal Total
6.
Nat Commun ; 12(1): 4164, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230493

RESUMO

Spi-1 Proto-Oncogene (SPI1) fusion genes are recurrently found in T-cell acute lymphoblastic leukemia (T-ALL) cases but are insufficient to drive leukemogenesis. Here we show that SPI1 fusions in combination with activating NRAS mutations drive an immature T-ALL in vivo using a conditional bone marrow transplant mouse model. Addition of the oncogenic fusion to the NRAS mutation also results in a higher leukemic stem cell frequency. Mechanistically, genetic deletion of the ß-catenin binding domain within Transcription factor 7 (TCF7)-SPI1 or use of a TCF/ß-catenin interaction antagonist abolishes the oncogenic activity of the fusion. Targeting the TCF7-SPI1 fusion in vivo with a doxycycline-inducible knockdown results in increased differentiation. Moreover, both pharmacological and genetic inhibition lead to down-regulation of SPI1 targets. Together, our results reveal an example where TCF7-SPI1 leukemia is vulnerable to pharmacological targeting of the TCF/ß-catenin interaction.


Assuntos
GTP Fosfo-Hidrolases/metabolismo , Proteínas de Membrana/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fator 1 de Transcrição de Linfócitos T/metabolismo , Transativadores/metabolismo , beta Catenina/metabolismo , Animais , Transplante de Medula Óssea , Carcinogênese/genética , Modelos Animais de Doenças , Feminino , GTP Fosfo-Hidrolases/genética , Células HEK293 , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Oncogenes , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteínas Proto-Oncogênicas/genética , Fator 1 de Transcrição de Linfócitos T/genética , Linfócitos T/metabolismo , Transativadores/genética , Transcriptoma , beta Catenina/genética
7.
Medicine (Baltimore) ; 100(25): e26330, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160396

RESUMO

PURPOSE: This systematic review aimed to identify the available evidence regarding the comparative effectiveness and safety of various operative treatments in adult patients with osteochondral lesions of the talus (OLT). MATERIALS AND METHODS: The PubMed, Embase, ISI Web of Knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date to September 2019. Two reviewers selected the randomized controlled trials (RCTs) and non-RCTs assessing the comparative effectiveness and safety of various operative treatments for OLT. The meta-analysis was performed using Revman 5.3. RESULTS: Eight studies (1 RCT and 7 non-RCTs) with 375 patients were included in this review. The difference in the American Orthopaedic Foot and Ankle Society (AOFAS) score between the cartilage repair and replacement was not significant. The cartilage regeneration with or without cartilage repair had significant superiority in improving the AOFAS score compared with the cartilage repair. The difference in the magnetic resonance observation of cartilage repair tissue score between the cartilage repair and replacement and between cartilage repair and cartilage repair plus regeneration was significant. CONCLUSIONS: Cartilage regeneration and cartilage repair plus regeneration had significant superiority in improving the ankle function and radiological evaluation of OLT, although the trials included did not have high-level evidence. Moreover, which treatment between the 2 was safer could not be addressed in this review as most of the trials did not report the safety outcome. Further studies are needed to define the best surgical option for treating OLT.


Assuntos
Articulação do Tornozelo/cirurgia , Cartilagem Articular/cirurgia , Osteocondrite/cirurgia , Tálus/cirurgia , Adulto , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/patologia , Artroplastia Subcondral/estatística & dados numéricos , Transplante de Medula Óssea/estatística & dados numéricos , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Condrócitos/transplante , Humanos , Imageamento por Ressonância Magnética , Ensaios Clínicos Controlados não Aleatórios como Assunto , Osteocondrite/diagnóstico , Osteocondrite/patologia , Plasma Rico em Plaquetas , Ensaios Clínicos Controlados Aleatórios como Assunto , Tálus/diagnóstico por imagem , Tálus/patologia , Transplante Autólogo/métodos , Transplante Autólogo/estatística & dados numéricos , Resultado do Tratamento
10.
Ann Hematol ; 100(8): 2071-2078, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34148110

RESUMO

ABO incompatibility is not a barrier to allogeneic stem cell transplant but may result in acute hemolytic reactions. As stem cell product manipulation is cumbersome, we are reporting the effectiveness and safety of donor-type red cell infusion as a method of reducing acute hemolytic reaction while using marrow as stem cell source. In major ABO-mismatched bone marrow transplants, manipulation of marrow product requires expertise and expensive equipment, which may not be readily available to transplant centers in low- and middle-income regions. The aim behind our study is to report a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants. We retrospectively analyzed 303 consecutive allogeneic bone marrow transplants (BMTs) for beta thalassemia major, between August 2015 and March 2020, with either major (n = 41) or bidirectional (n = 14) mismatches. When isohemagglutinin titers were 1:32 or higher, donor-type packed red blood cell was divided into 4 aliquots, irradiated and administered over 4 days at incremental volumes. Patients were observed for hemolytic reaction, and if no reaction, bone marrow was infused without manipulation. Out of 55 patients, 20 received donor-type blood infusion. Twelve patients showed evidence of mild hemolysis. None developed severe hemolytic or anaphylactic reaction. Titers were rechecked in 14 patients and all had reduction in titers, except for one. Our experience demonstrated that donor-type PRBC infusion is safe and effective in preventing acute hemolysis in major ABO-mismatched stem cell transplants even with bone marrow as graft source.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos/sangue , Transplante de Medula Óssea/métodos , Transfusão de Eritrócitos/métodos , Hemaglutininas/sangue , Adolescente , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Feminino , Hemólise , Humanos , Masculino , Estudos Retrospectivos , Doadores de Tecidos , Transplante Homólogo
11.
J Stroke Cerebrovasc Dis ; 30(8): 105932, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34148020

RESUMO

OBJECTIVES: Bone marrow mononuclear cells (BM-MNC) show a significant therapeutic effect in combination with training even in the chronic phase of stroke. However, the mechanism of this combination therapy has not been investigated. Here, we examined its effects on brain metabolism in chronic stroke mice. MATERIALS AND METHODS: BM-MNC (1x105 cells in 100 µL of phosphate-buffered saline) were intravenously transplanted at 4 weeks (chronic stage) after the middle cerebral artery occlusion. At 3 h and 10 weeks after the administration of BM-MNC, we evaluated transcription changes of the metabolism-related genes, hypoxia inducible factor 1-α (Hif-1α), prolyl hydroxylase 3 (Phd3), pyruvate dehydrogenase kinase 1 (Pdk1), Na+/K+-ATPase (Atp1α1‒3), connexins, glucose transporters, and monocarboxylate transporters, in the brain during chronic phase of stroke using quantitative polymerase chain reaction. RESULTS: The results showed transcriptional activation of the metabolism-related genes in the contralateral cortex at 3 h after BM-MNC transplantation. Behavioral tests were performed after cell therapy, and the brain metabolism of mice with improved motor function was examined at 10 weeks after cell therapy. The therapeutic efficacy of the combination therapy with BM-MNC transplantation and training was evident in the form of transcriptional activation of ipsilateral anterior cerebral artery (ACA) cortex. CONCLUSIONS: BM-MNC transplantation combined with training for chronic stroke activated gene expression in both the ipsilateral and the contralateral side.


Assuntos
Células da Medula Óssea/metabolismo , Transplante de Medula Óssea , Encéfalo/metabolismo , Metabolismo Energético , Infarto da Artéria Cerebral Média/terapia , Condicionamento Físico Animal , Animais , Comportamento Animal , Encéfalo/fisiopatologia , Doença Crônica , Terapia Combinada , Conexinas/genética , Conexinas/metabolismo , Modelos Animais de Doenças , Metabolismo Energético/genética , Regulação da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Camundongos Endogâmicos C57BL , Camundongos SCID , Atividade Motora , Recuperação de Função Fisiológica , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Transcrição Genética
12.
Rev Med Liege ; 76(5-6): 470-475, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-34080382

RESUMO

Acute leukemias are a heterogeneous group of malignant hemopathies which are subdivided according to the cytological orientation of the pathological blast cell into lymphoblastic (ALL) and myeloblastic (AML) acute leukemias. Recent advances in the biological and genetic understanding of these diseases have led to improved treatments. Specific chemotherapy treatment or so-called «targeted¼ treatments, advances in bone marrow transplantation and better supportive care have gradually improved the prognosis. This review, focused on the adult patient, aims to describe recent progress in terms of diagnosis, prognostic markers and therapy.


Assuntos
Leucemia Mieloide Aguda , Doença Aguda , Adulto , Transplante de Medula Óssea , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Prognóstico
13.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063118

RESUMO

Mesenchymal stem cells (MSCs) have been widely used in therapeutic applications for many decades. However, more and more evidence suggests that factors such as the site of origin and pre-implantation treatment have a crucial impact on the result. This study investigates the role of freshly isolated MSCs in the lacrimal gland after allogeneic transplantation. For this purpose, MSCs from transgenic GFP mice were isolated and transplanted into allogeneic and syngeneic recipients. While the syngeneic MSCs maintained a spherical shape, allogeneic MSCs engrafted into the tissue as spindle-shaped cells in the interstitial stroma. Furthermore, the MSCs produced collagen type I in more than 85% to 95% of the detected GFP+ MSCs in the recipients of both models, supposedly contributing to pathogenic fibrosis in allogeneic recipients compared to syngeneic models. These findings indicate that allogeneic MSCs act completely differently from syngeneic MSCs, highlighting the importance of understanding the exact mechanisms behind MSCs.


Assuntos
Transplante de Medula Óssea , Colágeno Tipo I/biossíntese , Células-Tronco Mesenquimais/metabolismo , Animais , Aparelho Lacrimal/citologia , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Transplante Homólogo , Transplante Isogênico
14.
Nat Commun ; 12(1): 3568, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117255

RESUMO

Bone marrow (BM) chimeric mice are a valuable tool in the field of immunology, with the genetic manipulation of donor cells widely used to study gene function under physiological and pathological settings. To date, however, BM chimera protocols require myeloablative conditioning of recipient mice, which dramatically alters steady-state hematopoiesis. Additionally, most protocols use fluorescence-activated cell sorting (FACS) of hematopoietic stem/progenitor cells (HSPCs) for ex vivo genetic manipulation. Here, we describe our development of cell culture techniques for the enrichment of functional HSPCs from mouse BM without the use of FACS purification. Furthermore, the large number of HSPCs derived from these cultures generate BM chimeric mice without irradiation. These HSPC cultures can also be genetically manipulated by viral transduction, to allow for doxycycline-inducible transgene expression in donor-derived immune cells within non-conditioned immunocompetent recipients. This technique is therefore expected to overcome current limitations in mouse transplantation models.


Assuntos
Transplante de Medula Óssea , Medula Óssea/metabolismo , Quimera/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Animais , Células da Medula Óssea , Técnicas de Transferência de Genes , Engenharia Genética , Terapia Genética , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quimeras de Transplante
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(5): 449-457, 2021 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34148880

RESUMO

OBJECTIVES: To establish mouse bone marrow transplantation by pretreatment with chemotherapy, and to explore the dynamic changes of immune cells in the early stage of allogeneic transplantation in the spleen of mice. METHODS: Mice were divided into 4 groups (80 mg/kg group, 100 mg/kg group, 120 mg/kg group, and 150 mg/kg group) according to the difference in dose of busulfan. The mice were treated with busulfan and cyclophosphamide combined chemotherapy, and the appropriate dosage was determined by evaluating the myeloablative effect and drug toxicity. According to the type of the genetic transplantation, the mice were also divided into 4 groups: An allogeneic transplantation group, a homogenic transplantation group, a chemotherapy alone group, and a normal control group. The mice were pretreated with busulfan and cyclophosphamide before bone marrow transplantation. In the allogeneic transplantation group, the suspension of splenocytes was prepared at the first day, the 3rd day, the 5th day, and the 8th day after transplantation for flow cytometry detection, and the dynamic changes of splenic immune cells were analyzed. The homogeneic transplantation group served as the concurrent control, the normal control group served as the control of basic value of spleen immune cells, and the chemotherapy alone group was used to evaluate the myeloablative effect. RESULTS: 1) The optimal dose of busulfan was 100 mg/kg. The combination of busulfan and cyclophosphamide can restore the hematopoiesis of transplanted mice, and the toxicity associated with pretreatment is small. 2) In the allogeneic transplantation group: The hematopoietic reconstitution and high donor chimerism rate were achieved after transplantation. In the early phase of bone marrow transplantation, the T lymphocytes were the main cell group, while the recovery of B lymphocytes was relatively delayed. The dendritic cells and natural killer cells from donors were the earliest cells to recover and achieve high chimerism rate compared with T cells and B cells. Most T cells were in the initial T cell state within 5 days after allogeneic transplantation. However, in the 5th day after transplantation, these cells were mainly in the effective memory phenotype. The reconstruction of donor-derived naive T cells was slow, but the reconstruction of donor-derived effective memory T cells and regulatory T cells was relatively fast. 3) In the homogeneic transplantation group: The mice could recover hematopoiesis and the recovery of B lymphocytes was delayed. 4) In the chemotherapy alone group: All mice died in 12-15 days after chemotherapy, and the peripheral blood routine showed pancytopenia before death. CONCLUSIONS: Pretreatment with chemotherapy can successfully establish the mouse model of bone marrow transplantation. There are difference in the proportion of T cells, B cells, natural killer cells, dendritic cells, effector memory T cells, initial T cells, and regulatory T cells after transplantation, and the relationship between donor and recipient is also changed.


Assuntos
Transplante de Medula Óssea , Bussulfano , Animais , Células da Medula Óssea , Proliferação de Células , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Transplante Homólogo
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 931-936, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105496

RESUMO

OBJECTIVE: To explore the kinetics of infiltrated T cell in murine acute graft-versus-host disease (aGVHD) target organs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its relationship with tissue pathological damage and aGVHD progress. METHODS: Male C57BL/6 (H-2Kb) mice at age of 8-10 weeks were selected as donors, from which splenic cells and bone marrow cells were isolated. And 10-12 weeks of BALB/c (H-2Kd) male mice which received 7.5 Gy total body irradiation (TBI) were recipients to transplant. Recipients were randomly divided into allogeneic bone marrow transplantation (BMT) group and BMT+T group, which were transplanted bone marrow cells with or without splenic cells, respectively. All recipients were daily monitored and the dynamic changes of the body weights along with clinical scores of aGVHD were detected. HE staining was used to investigate the pathological damage and score of aGVHD target organs. The number of infiltrated CD3+ T cells in target organs was numerated and statistically analyzed after immunohistochemistry staining on day 7, 14, 28, 40 and 47 after transplantation. RESULTS: Compared with BMT group, the number of infiltrated T cells in aGVHD target organs including liver, lung and gut increased since day 7 in BMT+T group (P<0.05). On day 14, 28, 40 and 47 after transplantation, more infiltrated CD3+ T cells were detected in target tissues of mice in BMT+T group than those in BMT group (P<0.05). Higher clinical score and histopathological score of target organs in aGVHD mice were detected (P<0.05). Positive correlation was found in the number of liver infiltrated T cells and pathological damage, and the numbers of infiltrated CD3+ T cells in gut were positively related to aGVHD clinical scores. CONCLUSION: Pathological damage of aGVHD target organs is induced by CD3+ T cell infiltration, and the number of infiltrated T cell may be an important evaluated index of aGVHD severity.


Assuntos
Doença Enxerto-Hospedeiro , Animais , Transplante de Medula Óssea , Cinética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Linfócitos T , Transplante Homólogo
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 937-943, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105497

RESUMO

OBJECTIVE: To establish the aGVHD mouse model,and investigate the regulatory effect and its mechanism of low-dose GSI combined with BMSC on aGVHD mice. METHODS: C57BL/6 (H-2b) and BALB/c (H-2d) were selected as donor and recipient of allogeneic transplantation to establish the aGVHD mouse model. BALB/c mice were randomly divided into 6 groups, which were the bone marrow cell infusion after irradiation (BM) group; the bone marrow cells + spleen cells after irradiation (BM+SC) group; the bone marrow cells + spleen cells + DMSO (BM+SC+DMSO) (transplant control) group; bone marrow cells + splenocytes +GSI after irradiation (BM+SC+GSI) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal infusion after irradiation cell (BM+SC+BMSC) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal cells +GSI infused after irradiation (BM+SC+BMSC+GSI) group. The mice in the two groups containing GSI were intraperitoneally injected with GSI at 5 µmol/kg on day 1, 2, and 3 after transplantation with DMSO as a control. The general conditions, survival time and hematopoietic recovery of mice were observed, cytokines were detected by ELISA, and histopathological changes were detected by immunohistochemistry. The effects of low-dose GSI combined with BMSC on hematopoietic reconstruction and aGVHD development after allo-BMT were investigated. RESULTS: The survival rate of the mice in BM+SC+BMSC+GSI combination group was 80% during the observation period, which was significantly higher than that in the other groups; the incidence of aGVHD was reduced in the BMSC GSI or their combination groups after 21 days of transplantation. GSI could partly promote the recovery of leukocytes, and show no significant delayed effect on the recovery platelets. Moreover, the level of Th1 cytokines (IFN-γ) in BM+SC+BMSC+GSI combined group was lower than that in BM+SC+GSI group (P<0.01), the level of Th2 cytokines (IL-4) in the combination group was higher than that in BM+SC+GSI group (P<0.01), also the level of IL-17 was significantly lower than that in the corresponding control group (P<0.001). CONCLUSION: Low dose GSI combined with BMSC can promote hematopoietic reconstruction and regulate cytokines secretion including IFN-γ, IL-4 and IL-17. GSI combined with BMSC achieve the goal of synergistically inhibiting the occurrence and progression of aGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Secretases da Proteína Precursora do Amiloide , Animais , Transplante de Medula Óssea , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
18.
Aquichan ; 21(2): e2126, jun. 25, 2021.
Artigo em Inglês | LILACS, BDENF - Enfermagem, COLNAL | ID: biblio-1283793

RESUMO

Objetivo: evaluar y correlacionar la calidad de vida general y la función cognitiva de pacientes adultos con cáncer hematológico sometidos al trasplante de células madre hematopoyéticas autólogo y alogénico hasta tres años luego del tratamiento. Materiales y método: estudio longitudinal, observacional y analítico con 55 pacientes, en un hospital de referencia en Latinoamérica, de septiembre del 2013 a febrero del 2019, con el instrumento Quality of Life Questionnarie-Core 30, analizado con las pruebas coeficiente de correlación de Spearman y el Generalized Linear Mixed Model. Resultados: la calidad de vida general en el trasplante autólogo y alogénico presentaron descenso en la fase de pancitopenia (59,3 y 55,3, respectivamente). Hubo disfunción cognitiva en el grupo autólogo posteriormente al trasplante dos años (61,90) y el grupo alogénico (74), en la pancitopenia. En el grupo autólogo, se observa correlación positiva (0,76) y significativa (p < 0,04) entre el dominio cognitivo y la calidad de vida en el post-trasplante dos años. En el alogénico, hubo correlación positiva (0,55) y significativa (p < 0,00) desde el post-trasplante 180 días. Conclusiones: la calidad de vida y la función cognitiva presentan compromiso y hay correlación luego del trasplante de células madre hematopoyéticas para ambos grupos, autólogo y alogénico.


Objective: To assess and correlate overall quality of life and the cognitive function of adult patients with hematologic cancer subjected to autologous and allogeneic hematopoietic stem cell transplantations up to three years after treatment. Materials and method: A longitudinal, observational, and analytical study was conducted with 55 patients in a reference hospital in Latin America, from September 2013 to February 2019, with the Quality of Life Questionnaire-Core 30, analyzed with the Spearman's correlation coefficient and Generalized Linear Mixed Model tests. Results: Overall quality of life in autologous and allogeneic transplantations presented a decline in the pancytopenia phase (59.3 and 55.3, respectively). There was impairment of the cognitive function in the autologous group in post-transplantation after two years (61.90) and, in the allogeneic group (74), in pancytopenia. In the autologous group, a positive (0.76) and significant (p < 0.04) correlation is observed between the cognitive domain and quality of life in post-transplantation after two years. In the allogeneic group, there was a positive (0.55) and significant (p < 0.00) correlation from 180 days after transplantation. Conclusions: Quality of life and the cognitive function present impairment and there is a correlation after the hematopoietic stem cell transplantation for both groups: autologous and allogeneic.


Objetivo: avaliar e correlacionar a qualidade de vida geral e a função cognitiva de pacientes adultos com câncer hematológico submetidos ao transplante de células-tronco hematopoéticas autólogo e alogênico até três anos após o tratamento. Materiais e método: estudo longitudinal, observacional e analítico com 55 pacientes, num hospital de referência na América Latina, de setembro de 2013 a fevereiro de 2019, com o instrumento Quality of Life Questionnarie-Core 30, analisado com os testes coeficiente de correlação de Spearman e o Generalized Linear Mixed Model. Resultados: a qualidade de vida geral no transplante autólogo e alogênico apresentaram declínio na fase de pancitopenia (59,3 e 55,3, respectivamente). Houve comprometimento da função cognitiva no grupo autólogo no pós-transplante dois anos (61,90) e no grupo alogênico (74), na pancitopenia. Observa-se, no grupo autólogo, correlação positiva (0,76) e significativa (p < 0,04) entre o domínio cognitivo e a qualidade de vida no pós-transplante dois anos. No grupo alogênico, houve correlação positiva (0,55) e significativa (p < 0,00) a partir do pós-transplante 180 dias. Conclusões: a qualidade de vida e a função cognitiva apresentam comprometimento e há correlação após o transplante de células-tronco hematopoéticas para ambos os grupos, autólogo e alogênico.


Assuntos
Qualidade de Vida , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Disfunção Cognitiva , Neoplasias
19.
Methods Mol Biol ; 2308: 163-176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057723

RESUMO

Decade-long survival of plasma cells in the bone marrow has long been a puzzling matter. To understand how plasma cells are maintained and supported by survival-niches to account for lifelong antibody production demands new intravital imaging techniques that are able to follow up a single cell and their interaction with other cell types in situ. We achieved to successfully establish longitudinal imaging of the bone marrow (LIMB) that is based on an implantable endoscopic device. In this chapter, basic approaches on how to investigate plasma cell-stroma interaction and surgical implantation procedures are introduced.


Assuntos
Células da Medula Óssea/fisiologia , Medula Óssea/fisiologia , Microambiente Celular , Processamento de Imagem Assistida por Computador , Microscopia Intravital , Microscopia de Fluorescência por Excitação Multifotônica , Plasmócitos/fisiologia , Transferência Adotiva , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Transplante de Medula Óssea , Separação Celular , Genes Reporter , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Camundongos Transgênicos , Plasmócitos/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo
20.
Front Cell Infect Microbiol ; 11: 657245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968803

RESUMO

The long-term impact of viruses residing in the human bone marrow (BM) remains unexplored. However, chronic inflammatory processes driven by single or multiple viruses could significantly alter hematopoiesis and immune function. We performed a systematic analysis of the DNAs of 38 viruses in the BM. We detected, by quantitative PCRs and next-generation sequencing, viral DNA in 88.9% of the samples, up to five viruses in one individual. Included were, among others, several herpesviruses, hepatitis B virus, Merkel cell polyomavirus and, unprecedentedly, human papillomavirus 31. Given the reactivation and/or oncogenic potential of these viruses, their repercussion on hematopoietic and malignant disorders calls for careful examination. Furthermore, the implications of persistent infections on the engraftment, regenerative capacity, and outcomes of bone marrow transplantation deserve in-depth evaluation.


Assuntos
Transplante de Medula Óssea , Medula Óssea , DNA Viral , Vírus da Hepatite B , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
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