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Hematol., Transfus. Cell Ther. (Impr.) ; 44(1): 13-16, Jan.-Mar. 2022. ilus
Article in English | LILACS | ID: biblio-1364907


Abstract Introduction Soon after the onset of the SARS-CoV-2 pandemic, viral screening by nasopharyngeal swab became mandatory for allogeneic hematopoietic stem cell (HSC) donor eligibility. Methods We described our monocenter experience with allogeneic HSC donors from February 1 to the October 31, 2020 to verify whether the introduction of SARS-CoV-2 screening altered the donor eligibility and/or entailed a prolongation of the evaluation process. Results A total of 21 allogeneic HSC donors were screened during the above-mentioned period upon request by the local transplant physicians or by the Italian Bone Marrow Donor Registry; among the HSC donors (n = 17) who completed the eligibility process and further received the nasopharyngeal swab, all but one were negative for the presence of SARS-CoV-2. The positive donor remained asymptomatic for the whole duration of the infection, which lasted six weeks. However, he was temporarily excluded from donation. The median duration of the evaluation process was not significantly different, compared to the same period of 2019 (p-value = 0.11). Conclusion The mandatory SARS-CoV-2 screening in allogeneic HSC donors allowed for the detection of 6% positivity in this monocenter series over a 9-month period. Despite the inconvenience of this unexpected non-eligibility, the exclusion of a SARS-CoV-2 positive donor represented an important safety measure for the donor, with respect to a new and still partially unknown virus. The screening did not alter the length of the donor evaluation and thus, did not cause a delay in the eligibility process.

Humans , Male , Female , Adult , Middle Aged , Hematopoietic Stem Cells , SARS-CoV-2 , Tissue Donors , Mass Screening
Acta Pharmaceutica Sinica B ; (6): 678-691, 2022.
Article in English | WPRIM | ID: wpr-929319


Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.

Cienc. Salud (St. Domingo) ; 6(1): [55-64], ene.-abr. 2022. graf, tab
Article in Spanish | LILACS | ID: biblio-1366873


La Leucemia Mieloide Aguda es una enfermedad caracterizada por la alteración en la producción de células madre hematopoyéticas y la proliferación celular. Es más común en adultos; a pesar de ello solo se presenta en el 1 % en los Estados Unidos. Entre los 65-68 años se observa una mayor incidencia existiendo de 2-3 casos por cada año en 100.000 habitantes, siendo aproximadamente el 10 % de los cánceres de este tipo. Los diagnósticos más recomendados para esta enfermedad son los de carácter sanguíneo, la realización de citometrías de flujo en muestra de médula ósea. Según estudios, los análisis citogenéticos en un gran número de pacientes han demostrado translocaciones e inversiones en los cromosomas somáticos, mientras que solo una minoría tiene una organización de cromosomas somáticos balanceada. La terapia de consolidación se acompaña del trasplante de células madre hematopoyéticas, conocido como el trasplante alogénico, que puede ser potencialmente curativo en algunos pacientes.

The acute myeloid leukemia, is a disease which is a characterized by an irregular production of hematopoietic cells and cellular proliferation. It´s most common in adults, however only 1% of American adults will be diagnosed throughout their lives. Between the ages of 65-68 there is a high incidence with only 2-3 cases per 100.000 patients; making up only 10% of this type of cancer. It´s mainly diagnosed by using blood test, flow cytometry (on Bone Marrow samples). Some cytogenetic studies suggest that in a significant number of patients both somatic chromosomal inversion and translocation are present, while only a small percentage show no somatic chromosomal mutations. Consolidation therapy with a hematopoietic Stem Cells transplant, also known as a "allogenic transplant", can be potentially curative in some special cases.

Leukemia, Myeloid , Transplantation, Homologous
Article in Chinese | WPRIM | ID: wpr-847094


BACKGROUND: Muscle tissue plays an important role in completing exercise, maintaining body position and maintaining homeostasis in the body. Muscle quality assessment and intervention can help to improve the quality of life of patients and shorten the length of hospital stay, which has become a research hotspot in recent years. OBJECTIVE: To explore the related influencing factors of muscle mass decline by systematic assessment of limb muscle mass in patients undergoing allogeneic hematopoietic stem cell transplantation. METHODS: 146 patients who underwent allogeneic hematopoietic stem cell transplantation were selected as the study subjects. The general information questionnaire was used to collect patients’ age, sex, and education degree. Muscle mass was measured by bioelectrical impedance analysis. Patient’ body mass index, arm muscle circumference, triceps skinfold thickness, body fat rate, conditioning regimen, antithymocyte globuin dose, HLA matching, graft source, albumin, prealbumin and total protein, and ECOG score were collected. The t test, chi square test and binary logistic regression analysis were used to analyze appendicular skeletal muscle. The study was approved by the Ethics Committee of Guangzhou First People’s Hospital. All patients agreed to participate in the study and signed informed consent. RESULTS AND CONCLUSION: (1) Muscle mass loss was observed in 89 patients (60.9%) of allogeneic hematopoietic stem cell transplantation, including 51 males and 38 females. Compared with the reference values of the Chinese normal population, it was found that allogeneic hematopoietic stem cell transplantation patients showed lower levels of muscle mass, arm muscle circumference and triceps skinfold thickness, but body fat rate increased significantly, with statistically significant differences (P 0.05). (3) A single factor comparison of muscle mass showed that there were statistically significant differences in weight, body mass index, conditioning regimen and ECOG score (P < 0.05). Binary logistic regression showed that high body mass index was a protective factor of muscle mass in patients with allogeneic hematopoietic stem cell transplantation (OR=52.804, P < 0.05), and high ECOG score was a risk factor (OR=0.458, P < 0.05). (4) Results indicate that allogeneic hematopoietic stem cell transplantation patients generally have decreased muscle mass in their extremities, and muscle mass can reflect the nutritional status of patients earlier than blood biochemical indicators such as albumin, providing earlier warning for nutritional intervention. Therefore, early evaluation of skeletal muscle mass in allogeneic hematopoietic stem cell transplantation patients should be conducted.

Article in Chinese | WPRIM | ID: wpr-878706


The self-renewal and differentiation of hematopoietic stem cells(HSCs)are highly regulated by epigenetic modification,in which histone acetylation can activate or silence gene transcription.Histone deacetylase inhibitors(HDACIs)can inhibit the activity of histone deacetylase in HSCs to increase histone acetylation.A variety of HDACIs,such as trichostatin A and valproic acid,are used to expand HSCs in vitro,especially cord blood HSCs,combined with cytokines in serum-free culture to obtain more long-term repopulating cells.HDACIs promote the transcription of pluripotent genes related to stem cell self-renewal and inhibit the expression of genes related to differentiation,so as to promote the expansion and inhibit differentiation of HSCs.The expansion of cord blood HSCs by small molecular HDACIs in vitro is expected to improve the quantity of cord blood HSCs.The further research will focus on high-throughput screening for the most powerful HDACIs and the highly selective HDACIs,exploring the combination of epigenetic modifiers of different pathways.

Epigenesis, Genetic , Fetal Blood , Hematopoietic Stem Cells , Histone Deacetylase Inhibitors/pharmacology , Valproic Acid/pharmacology
Journal of Leukemia & Lymphoma ; (12): 505-508, 2021.
Article in Chinese | WPRIM | ID: wpr-907205


T-cell acute lymphoblastic leukemia (T-ALL) is derived from the malignant transformation and clonal proliferation of precursor T cells. T-ALL is usually associated with the genetic mutations and/or chromosomal translocation, thus causing the change of survival, proliferation and progenitor cell differentiation of T cells in T-cell development. Studies have shown that Wnt signaling pathway plays a key role in the regulation of hematopoietic stem cell and normal T-cell development, and it is also abnormally altered in T-ALL. This article reviews the research progress of the mechanism of Wnt signaling pathway in T-ALL development.

Chinese Journal of Biotechnology ; (12): 3945-3960, 2021.
Article in Chinese | WPRIM | ID: wpr-921478


The thymus is a pivotal immune organ of the human body, and it is the place where T cells differentiate and mature. The damage of thymus would easily induce autoimmune diseases and even malignant tumors. For years, researchers have been exploring the process of T cell development and revealing the mechanism of thymic injury and regeneration generally through the monolayer culture system of T cells in vitro. However, the classic monolayer culture system could neither reproduce the unique three-dimensional epithelial reticular structure of the thymus, nor provide the cytokines and growth factors required for the directed differentiation of hematopoietic stem cells into T cells. Thymic organoid technology utilizes cells with stem cell potential to simulate the anatomical structure of the thymus and the signaling pathway mediated by thymic epithelial cells in vitro through three-dimensional culture, which is particularly close to the microenvironment of the thymus in vivo. Thymic organoids show great potential in the study of T cell differentiation and development, thymus-related diseases, reconstruction of immune function, and cell therapy. This paper summarizes the methods for culturing thymic organoids, followed by comparing the advantages and disadvantages of the scaffolds used for culturing. The applications of thymic organoids in the disease model, tumor-targeting therapy, regenerative medicine, and organ transplantation were also discussed, with possible future research directions prospected.

Cell Differentiation , Epithelial Cells , Hematopoietic Stem Cells , Humans , Organoids , Regenerative Medicine , Thymus Gland
Rev. eletrônica enferm ; 23: 1-12, 2021.
Article in English, Portuguese | LILACS, BDENF | ID: biblio-1248185


Objetivou-se analisar o conceito de "Proteção" em pacientes submetidos ao transplante de células tronco hematopoiéticas e cor-relacionar com os elementos do diagnóstico de enfermagem "Proteção Ineficaz" proposto pela NANDA-I.Revisão integrativa da literatura, fundamentada no modelo de Análise de Conceito proposto por Walker e Avant. Realizada na Biblioteca Virtual em Saúde e as seguintes bases de dados: CINAHL, SCOPUS, PUBMED/MEDLINE, LILACS e Web of Science com recorte temporal de cinco anos. A amostra final foi composta por 16 artigos e pela identificação de três atributos definidores, 15 antecedentes e 11 consequentes.Conclusão:a análise de conceito pode contribuir para o refinamento e o aprimoramento do diagnóstico de en-fermagem "Proteção Ineficaz". Foi possível identificar uma outra definição, 10 antecedentes e 10 consequentes que não constam na NANDA-I, bem como a necessidade de revisar a definição e demais componentes do diagnóstico propostos pela taxonomia.

The objective was to analyze the "Protection" concept in patients undergoing hematopoietic stem cell transplantation and correlate it with elements of the "Ineffective Protection" nursing diagnosis proposed by NANDA-I. Integrative literature review based on the Concept Analysis model proposed by Walker and Avant and performed at the Virtual Health Library and CINAHL, SCOPUS, PUBMED/MEDLINE, LILACS and Web of Science databases within a five-year time frame . The final sample consisted of 16 articles and the identification of three defining attributes, 15 antecedents and 11 consequences. Conclusion: concept analysis can contribute to refine and improve the nursing diagnosis "Ineffective Protection". It was possible to identify another definition, 10 antecedents and 10 consequences that are not included in NANDA-I, as well as the need to revise the definition and other components of the diagnosis proposed by the taxonomy.

Hematopoietic Stem Cell Transplantation/adverse effects , Immunocompetence , Nursing Process
Rev. colomb. reumatol ; 27(supl.1): 126-134, Oct.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1341328


ABSTRACT The mesenchymal stromal cells (MSCs) are hematopoietic stem cells with high capacity of differentiation to other cellular lineages, depending on the microenvironment in which they live as well as on the interaction and signaling pathways they establish with the extracellular matrix. Several properties have been described in these cells: proangiogenic, antifibrotic and immunomodulatory. These properties are being studied as a therapeutic approach for autoimmune diseases such as cutaneous systemic sclerosis (SSc). SSc is a systemic chronic disease, with an approximate prevalence of 35.6 cases per 100,000 inhabitants in North America and of 0.02% in Colombia in 2018. There are two different clinical variants, diffuse and localized. In both variants an important skin involvement and a rapidly deterioration of organs is present, which can overshadow the clinical prognosis and increase the mortality. Options for the treatment of advanced diffuse SSc are scarce mainly targeting symptomatic control with little impact on the progression and mortality. Therefore, there is an increasing interest in new therapies like advanced cellular therapy with hematopoietic stem cells and stromal mesenchymal cells. This article reviews the information related to the use of stromal mesenchymal cells in patients with this disease.

RESUMEN Las células mesenquimales estromales son células madre no hematopoyéticas pluripotenciales con alta capacidad de derivación a diferentes linajes celulares, dependiendo tanto del microambiente en el que se encuentren, como de la interacción y señalización que establezcan con la matriz extracelular del entorno, esto ha permitido describir un potencial proangiogénico, antifibrótico e inmunomodulador, que ha sido blanco de investigación en enfermedades autoinmunes como la esclerosis sistêmica cutánea. Considerando que la esclerosis sistêmica cutánea es una enfermedad inflamatoria crónica, con una prevalencia estimada de 35,6 casos por cada 100.000 habitantes en Norte América y de 0,02% en nuestro país para el 2018, se caracteriza por presentar dos variables clínicas principalmente; una variante limitada y una variante difusa, presentando en ambas un compromiso extenso de piel y órganos que puede ser rápidamente progresivo y deteriorar el pronóstico de los pacientes que la padecen aumentando su mortalidad. Debido a que las opciones terapéuticas en esta entidad son limitadas y buscan únicamente el control de síntomas, pero con poco impacto en progresión y mortalidad, terapias celulares avanzadas han surgido como nuevas opciones terapéuticas incluyendo el trasplante de células madre hematopoyéticas y las células mesenquimales estromales. A continuación, se revisará acerca de la utilidad y evidencia de células mesenquimales estromales en pacientes con esta enfermedad.

Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Therapeutics , Stromal Cells , Patients , Scleroderma, Systemic , Autoimmune Diseases
Article in Chinese | WPRIM | ID: wpr-847633


BACKGROUND: Bone marrow failure is an important pathogenesis of aplastic anemia, and how to reverse bone marrow failure is an issue of concern. OBJECTIVE: To investigate the regulatory effect of angelica polysaccharide on the mitochondrial dysfunction in murine aplastic anemia. METHODS: Seventy-two ICR mice were randomly divided into control, model and treatment groups (n=24 per group). The mice in the latter two groups were used to establish the aplastic anemia models by60Co γ radiation, intraperitoneal injection of cyclophosphamide and intragastric administration of chloramphenicol, and were then given normal saline or 200 mg/kg angelica polysaccharide for 2 weeks, respectively. The control mice received no intervention. At 1, 7 and 14 days after modeling, peripheral blood cells and bone marrow mononuclear cells were counted, and mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy. After Lin- Sca-1+ c-Kit+ (LSK) cells were sorted from bone marrow cells, which were hematopoietic stem cells. The mitochondrial membrane potential, levels of reactive oxygen species, and the expression levels of Bcl 2, Bax, cleaved caspase-9, cleaved caspase-3 and p38 in LSK cells were detected. RESULTS AND CONCLUSION: Compared with the control group, in the model and treatment groups, there were obvious abnormalities in the peripheral blood routine test was the number of bone marrow mononuclear cells was decreased significantly, the mitochondrial number, mitochondrial membrane potential and Bcl 2/Bax ratio were decreased, and the level of reactive oxygen species and the expression of cleaved caspase-9, cleaved caspase-3 and p38 in LSK cells were significantly increased (P < 0.05). After angelica polysaccharide treatment, all above results were significantly improved as compared with the model group (P < 0.05). To conclude, angelica polysaccharide might improve hematopoietic function by up-regulating the mitochondrial membrane potential, increasing the mitochondrial membrane stability and reversing the levels of apoptotic factors.

Einstein (Säo Paulo) ; 18: eAO5075, 2020. tab
Article in English | LILACS | ID: biblio-1101100


ABSTRACT Objective To evaluate the nutritional risk factors in patients eligible for hematopoietic stem cell transplantation. Methods A cross-sectional, descriptive study conducted with patients recruited from an hematology outpatient clinic. Study variables included demographic and clinical data, patient-generated global subjective assessment findings, anthropometric indicators, food intake and oxidative stress levels. The level of significance was set at 5% (p<0.05). Results The sample comprised 72 patients, mean age of 48.93 years (14.5%). Multiple myeloma was the most prevalent condition (51.4%) in this sample. Most patients (55.6%) were overweight according to body mass index and at risk of cardiovascular disease according to waist circumference, conicity index and percentage of body fat. Sarcopenia was associated with risk of cardiovascular disease, hip-to-waist ratio (p=0.021), muscle strength depletion (p<0.001), food intake (p=0.023), reduced functional capacity (p=0.048), self-reported well-nourished status; p=0.044) and inadequate vitamin B6 (p=0.022) and manganese (p=0.026) intake. Elevated oxidative stress, detected in 33.3% of patients in this sample, was not associated with sarcopenia. Conclusion Most patients in this sample were overweight and sarcopenic. Lean mass depletion was associated with risk of cardiovascular disease, reduced muscle strength, food intake changes, reduced functional capacity, self-reported well-nourished status and inadequate intake of vitamin B6 and manganese, but not with oxidative stress.

RESUMO Objetivo Avaliar os fatores de riscos nutricionais em pacientes pré-transplante de célula-tronco hematopoiética. Métodos Estudo transversal, descritivo, realizado com pacientes de um ambulatório de hematologia. As variáveis estudadas foram demográficas, dados clínicos, avaliação subjetiva global produzida pelo próprio paciente, indicadores antropométricos, ingestão alimentar e estresse oxidativo. Os dados foram considerados estatisticamente significativos quando p<0,05. Resultados A amostra do estudo foi constituída por 72 pacientes, com média de idade de 48,93 (14,5%) anos e com mieloma múltiplo (51,4%) como a patologia mais prevalente. Conforme índice de massa corporal, 55,6% dos pacientes encontravam-se com excesso de peso. De acordo com a circunferência da cintura, índice de conicidade e percentual de gordura corporal, houve prevalência de risco para doença cardiovascular. A sarcopenia foi associada ao risco de doença cardiovascular pela relação cintura/quadril (p=0,021), depleção da força muscular (p<0,001), além da ingestão alimentar (p=0,023), da capacidade funcional reduzida (p=0,048) e do diagnóstico de "bem nutrido" (p=0,044), conforme a avaliação subjetiva global, e com consumo inadequado de vitamina B6 (p=0,022) e de manganês (p=0,026). Dentre os avaliados, 33,3% apresentaram estresse oxidativo elevado sem associação com sarcopenia. Conclusão Pacientes do pré-transplante se apresentam, em sua maioria, com excesso de peso, mas com sarcopenia, estando essa ausência de massa magra associada a risco de doença cardiovascular, depleção da força muscular, alteração da ingestão alimentar, redução da capacidade funcional, classificação de "bem nutrido", segundo a avaliação subjetiva global e consumo inadequado de vitamina B6 e manganês, não estando associada a estresse oxidativo.

Humans , Male , Female , Adult , Nutrition Assessment , Risk Assessment/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Energy Intake/physiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Anthropometry , Nutritional Status/physiology , Cross-Sectional Studies , Risk Factors , Oxidative Stress/physiology , Eating/physiology , Overweight/complications , Overweight/physiopathology , Muscle Strength/physiology , Sarcopenia/complications , Sarcopenia/physiopathology , Middle Aged , Multiple Myeloma/surgery , Multiple Myeloma/physiopathology
Hematol., Transfus. Cell Ther. (Impr.) ; 41(4): 285-291, Oct.-Dec. 2019. tab
Article in English | LILACS | ID: biblio-1056247


ABSTRACT While first-line induction therapy for patients with multiple myeloma has changed over the years, autologous hematopoietic stem cell transplantation still plays a significant role, improving both depth of response and progression-free survival of myeloma patients. Our 25-year experience in mobilizing hematopoietic stem and progenitor cells for 472 transplant-eligible myeloma patients was retrospectively reviewed. Patients were stratified according to the remission induction therapy received, and the outcomes were compared among the cohorts that received vincristine, adriamycin and dexamethasone (VAD) (n = 232), bortezomib and dexamethasone (BD) (n = 86), cyclophosphamide, bortezomib and dexamethasone (CyBorD) (n = 82) and other regimens (n = 67). Cyclophosphamide plus granulocyte colony-stimulating factor was the predominant mobilization regimen given. A greater number of CD34+ cells (9.9 × 10E6/kg, p = 0.026) was collected with less hospital admissions in BD patients (13%, p = 0.001), when compared to those receiving VAD (7.5 × 10E6/kg, 29%), CyBorD (7.6 × 10E6/kg, 19%), or other regimens (7.9 × 10E6/kg, 36%). Induction therapy did not influence the overall rate of unscheduled visits or the length of hospitalization because of complications following mobilization. The myeloma response was not significantly deepened following the cyclophosphamide administered for mobilization. This analysis demonstrates the importance of monitoring the impact of initial treatment on downstream procedures such as stem cell mobilization and collection.

Humans , Male , Female , Stem Cells , Remission Induction , Hematopoietic Stem Cells , Cyclophosphamide , Multiple Myeloma , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cell Mobilization
Article in English | WPRIM | ID: wpr-764061


BACKGROUND AND OBJECTIVE: The characteristics of human hematopoietic stem cells are conditioned by the microenvironment of the bone marrow, where they interact with other cell populations, such as mesenchymal stem cells and endothelial cells; however, the study of this microenvironment is complex. The objective of this work was to develop a 3D culture system by magnetic levitation that imitates the microenvironment of human HSC. METHODS AND RESULTS: Human bone marrow-mesenchymal stem cells, umbilical cord blood-hematopoietic stem cells and a non-tumoral endothelial cell line (CC2811, Lonza®) were used to develop organotypic multicellular spheres by the magnetic levitation method. We obtained viable structures with an average sphericity index greater than 0.6, an average volume of 0.5 mm3 and a percentage of aggregation greater than 70%. Histological studies of the organotypic multicellular spheres used hematoxylin and eosin stains, and an evaluation of vimentin expression by means of immunohistochemistry demonstrated an organized internal structure without picnotic cells and a high expression of vimentin. The functional capacity of human hematopoietic stem cells after organotypic multicellular spheres culture was evaluated by multipotency tests, and it was demonstrated that 3D structures without exogenous Flt3L are autonomous in the maintenance of multipotency of human hematopoietic stem cells. CONCLUSIONS: We developed organotypic multicellular spheres from normal human cells that mimic the microenvironment of the human hematopoietic stem cells. These structures are the prototype for the development of complex organoids that allow the further study of the biology of normal human stem cells and their potential in regenerative medicine.

Biology , Bone Marrow , Coloring Agents , Endothelial Cells , Eosine Yellowish-(YS) , Hematopoietic Stem Cells , Hematoxylin , Humans , Immunohistochemistry , Mesenchymal Stem Cells , Methods , Organoids , Regenerative Medicine , Stem Cells , Umbilical Cord , Vimentin
Article in Chinese | WPRIM | ID: wpr-815997


Besides supporting the normal hematopoiesis tissue, hematopoietic microenvironment has also been found to support malignant hematopoietic diseases and even play a role in the initiation and development of the diseases. Here we reviewed the function of hematopoietic microenvironment in physiological or pathological state, as well as its possible potential role in the initiation or development of the myeloproliterative neoplasms.

Immune Network ; : e12-2019.
Article in English | WPRIM | ID: wpr-740216


Hematopoietic stem cells (HSCs) in bone marrow are pluripotent cells that can constitute the hematopoiesis system through self-renewal and differentiation into immune cells and red blood cells. To ensure a competent hematopoietic system for life, the maintenance of HSCs is tightly regulated. Although autophagy, a self-degradation pathway for cell homeostasis, is essential for hematopoiesis, the role of autophagy key protein Atg5 in HSCs has not been thoroughly investigated. In this study, we found that Atg5 deficiency in hematopoietic cells causes survival defects, resulting in severe lymphopenia and anemia in mice. In addition, the absolute numbers of HSCs and multiple-lineage progenitor cells were significantly decreased, and abnormal erythroid development resulted in reduced erythrocytes in blood of Vav_Atg5(−/−) mice. The proliferation of Lin⁻Sca-1⁺c-Kit⁺ HSCs was aberrant in bone marrow of Vav_Atg5(−/−) mice, and mature progenitors and terminally differentiated cells were also significantly altered. Furthermore, the reconstitution ability of HSCs in bone marrow chimeric mice was significantly decreased in the presence of Atg5 deficiency in HSCs. Mechanistically, impairment of autophagy-mediated clearance of damaged mitochondria was the underlying cause of the HSC functional defects. Taken together, these results define the crucial role of Atg5 in the maintenance and the reconstitution ability of HSCs.

Anemia , Animals , Autophagy , Bone Marrow , Erythrocytes , Hematopoiesis , Hematopoietic Stem Cells , Hematopoietic System , Homeostasis , Lymphopenia , Mice , Mitochondria , Stem Cells
Article in Chinese | WPRIM | ID: wpr-851446


Objective To explore the effects of the combination of main active components of Astragalus membranaceus and Angelica sinensis such as astragaloside IV, formononetin, calycosin, campanulin, ferulic acid on aging hematopoietic stem cells (HSCs), and clarify its mechanism through cell cycle regulation. Methods The aging model of HSCs in mice was established with three butyl hydrogen peroxide (t-BHP) to research the effects of five active components of different concentrations on the senescence and the proliferation of HSCs, and seek the main active components which could promote cell proliferation. Finally, HSCs aging model was used to prepare the drug-containing plasm of A. membranaceus combined with A. sinensis at 1:1 ratio. Furthermore, blank control group, model group, blank plasma group, ferulic acid group, astragaloside IV group, formononetin group, calycosin group, calycosin glycoside group, combination group of main active components, drug-containing plasma group of A. membranaceus combined with A. sinensis at 1:1 ratio were acted on aging cells, HSCs senescence rate was tested by SA-β-galactosidase staining and cell proliferation rate was measured by CCK-8 method, cell cycle distribution was determined by flow cytometry, and the protein expression of Cyclin D1 and cyclin dependent kinase 4 (CDK4) were detected by Western blotting. Results Ferulic acid, astragaloside IV, and formononetin significantly promoted the proliferation of aging HSCs and decreased the positive rate of senescent cells, but the effects of calycosin and calycosin glycoside on HSCs proliferation and the positive rate of senescent cells were not significant. The orthogonal experiment showed that the combination of five active components that ferulic acid, formononetin, astragaloside IV were taken as basic factors, and calycosin and calycosin glycoside were taken as secondary factors, had the strongest effect on promoting cell proliferation and decreasing the positive rate of senescent cells. Ferulic acid, astragaloside IV, formononetin, active component combination and drug-containing plasma decreased the positive rate of senescent cells, down-regulated G0/G1 phase cells while up-regulated G2/M + S phase cells, and increased the expression of Cyclin D1 and CDK4 proteins. The above effects in the active component combination group and the drug-containing plasma group were the best. Conclusion The main active components of A. membranaceus and A. sinensis such as ferulic acid, astragaloside IV, and formononetin can promote the proliferation and improve the senescent of aging HSCs, however, calycosin and calycosin glycoside have no obvious effect. The effect of promoting the proliferation is the strongest on aging HSCs when five active components are combined, and the combination can improve HSCs senescence, enhance the transformation of HSCs from static stage to proliferative stage. The main active components and the combination of A. membranaceus and A. sinensis can promote HSCs proliferation and antagonize HSCs senescent, which may be related to regulating the expression of cell cycle related proteins and promoting the transformation of cell cycle.

Article in English | WPRIM | ID: wpr-785716


Obesity, diabetes, and cardiovascular diseases are increasing rapidly worldwide and it is therefore important to know the effect of exercise and medications for diabetes and obesity on adult stem cells. Adult stem cells play a major role in remodeling and tissue regeneration. In this review we will focus mainly on two adult stem/progenitor cells such as endothelial progenitor cells and mesenchymal stromal cells in relation to aerobic exercise and diabetes medications, both of which can alter the course of regeneration and tissue remodelling. These two adult precursor and stem cells are easily obtained from peripheral blood or adipose tissue depots, as the case may be and are precursors to endothelium and mesenchymal tissue (fat, bone, muscle, and cartilage). They both are key players in maintenance of cardiovascular and metabolic homeostasis and can act also as useful biomarkers.

Adipose Tissue , Adult Stem Cells , Adult , Biomarkers , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Endothelial Progenitor Cells , Endothelium , Exercise , Hematopoietic Stem Cells , Homeostasis , Humans , Mesenchymal Stem Cells , Obesity , Regeneration , Stem Cells
Braz. j. med. biol. res ; 52(1): e7784, 2019. tab, graf
Article in English | LILACS | ID: biblio-974264


Myelofibrosis (MF) is characterized by increased circulating hematopoietic progenitor cells (HPCs), abnormal cytokine levels, and the survival advantage of neoplastic progenitors over their normal counterparts, which leads to progressive disappearance of polyclonal hematopoiesis. CD47 is a surface glycoprotein with many functions, such as acting as a phagocytosis inhibitor of the expressing cell, that is increased in normal hematopoietic stem and progenitor cells mobilized into the blood and several human cancer-initiating cells, such as in acute myeloid leukemia. We compared CD47 expression in hematopoietic stem and progenitor cells of patients with MF and controls and found it to be decreased in progenitors of MF. Exposure of control HPCs to the cytokines transforming growth factor β and stromal-derived factor 1, which are important regulators of hematopoietic stem cell cycling and are overexpressed in patients with MF, did not modulate CD47 expression.

Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Hematopoietic Stem Cells/metabolism , CD47 Antigen/metabolism , Primary Myelofibrosis/metabolism , Case-Control Studies , Transforming Growth Factor beta/metabolism , Chemokine CXCL12/metabolism , Primary Myelofibrosis/genetics
Texto & contexto enferm ; 28: e20180010, 2019. tab, graf
Article in English | LILACS, BDENF | ID: biblio-1004805


ABSTRACT Objective: to construct a protocol of nursing care to the patient on day zero of hematopoietic stem cell transplantation. Method: a convergent care research was developed from August to December 2016 in a Bone Marrow Transplant Service. The participants were twenty-two nurses from this service. The technique of data collection used was discussion groups. For the analysis the following steps were taken: transcription of the data, highlighting the suggestions of the participants; distribution of contributions by theme, for synthesis of the elements in a coherent whole, scientific evidence and contributions of the participants; and construction of the protocol, with refinement and approval of the final version by nurses. Results: the protocol, guides nursing care to be provided by the nurse on day zero of hematopoietic stem cell transplantation, according to the infusion mode: fresh and cryopreserved-thawed. These precautions aim to prevent, identify and intervene early in complications related to cell infusion. Conclusion: the protocol, product of the research, was elaborated in the union of scientific evidences, with the reality of the service and the experience of the participating nurses. The utilization of the methodological steps of convergent care research was a facilitator, because, as it presupposes, it provided the union of care practice with scientific research. The participation of nurses in the construction and approval of the protocol enabled the subsequent implementation and use of this tool in nursing service.

RESUMEN Objetivo: construir un protocolo de cuidados de enfermería al paciente en el día cero del transplante de células madre hematopoyéticas. Método: se trata de una investigación convergente asistencial, desarrollada de agosto a diciembre de 2016 en un Servicio de trasplante de médula ósea. Los participantes fueron veintidós enfermeros de este servicio. La técnica de recolección de datos utilizada fue grupos de discusión. Para el análisis se siguieron las etapas: transcripción de los datos, con destaque de las sugerencias de los participantes; distribución de las contribuciones por temática, para síntesis de los elementos en un todo coherente, evidencias científicas y contribuciones de los participantes; y la construcción del protocolo, con refinamiento y aprobación de la versión final por los enfermeros. Resultados: el protocolo, orienta cuidados de enfermería a ser prestados por el enfermero en el día cero del transplante de células madre hematopoyéticas, según la modalidad de infusión: fresca y criopreservada-descongelada. Estos cuidados tienen como objetivo prevenir, identificar e intervenir precozmente en las complicaciones relacionadas con la infusión de las células. Conclusión: el protocolo, producto de la investigación, fue elaborado en la unión de evidencias científicas, con la realidad del servicio y la experiencia / vivencia de los enfermeros participantes. La utilización de los pasos metodológicos de la investigación convergente asistencial fue un facilitador, pues, como presupone, proporcionó la unión de la práctica asistencial con la investigación científica. La participación de los enfermeros en la construcción y aprobación del protocolo posibilitó la posterior implantación y utilización de este instrumento en el servicio de enfermería.

RESUMO Objetivo: construir um protocolo de cuidados de enfermagem ao paciente no dia zero do transplante de células-tronco hematopoéticas. Método: trata-se de pesquisa convergente assistencial, desenvolvida de agosto a dezembro de 2016 em um Serviço de Transplante de Medula Óssea. Os participantes foram vinte e dois enfermeiros deste serviço. A técnica de coleta de dados utilizada foi grupos de discussão. Para a análise seguiu-se as etapas: transcrição dos dados, com destaque das sugestões dos participantes; distribuição das contribuições por temática, para síntese dos elementos num todo coerente, evidências científicas e contribuições dos participantes; e construção do protocolo, com refinamento e aprovação da versão final pelos enfermeiros. Resultados: o protocolo orienta os cuidados de enfermagem a serem prestados pelo enfermeiro no dia zero do transplante de células-tronco hematopoéticas, conforme a modalidade de infusão: fresca e criopreservada-descongelada. Estes cuidados visam prevenir, identificar e intervir precocemente nas complicações relacionadas à infusão das células. Conclusão: o protocolo, produto da pesquisa, foi elaborado na união de evidências científicas, com a realidade do serviço e a experiência/vivência dos enfermeiros participantes. A utilização dos passos metodológicos da pesquisa convergente assistencial foi um facilitador, pois, como pressupõe, proporcionou a união da prática assistencial com a pesquisa científica. A participação dos enfermeiros na construção e aprovação do protocolo possibilitou a posterior implantação e utilização deste instrumento no serviço de enfermagem.

Humans , Hematopoietic Stem Cells , Nursing , Hematopoietic Stem Cell Transplantation , Guidelines as Topic , Nursing Assessment , Nursing Care
Med. infant ; 25(1): 26-31, marzo 2018. tab
Article in Spanish | LILACS | ID: biblio-883475


Introducción: El Trasplante alogénico de células progenitoras hematopoyéticas (TCPH) se asocia a una lenta recuperación de sistema inmune, lo que predispone a sus receptores a presentar múltiples complicaciones infecciosas. En este trabajo se analizan las infecciones virales de una cohorte retrospectiva. Material y métodos: se revisó la base de datos del servicio y se registraron las infecciones virales del periodo 2012-2016. Resultados: n 215. El 91% de los receptores y el 70% de los donantes eran CMV positivos antes del trasplante, el 47% de os receptores presentó reactivación de CMV y el 10% enfermedad, con una mortalidad directa del 3,1%. El 87% de los receptores y el 70% de los donantes tenían serología para EBV y el 13% tuvieron una reactivación con una carga viral > 20.000 copias/ml. El 11% de los pac tuvieron enfermedad por Herpes zoster, el 6% por Herpes 6 y el 5% por Herpes simple. Se detectó infección por adenovirus en el 25% de los pacientes, siendo el compromiso más frecuente el digestivo, seguido de la infección respiratoria baja. La mortalidad directa por adenovirus fue 5,1%. Se registraron 41 episodios de infección respiratoria aguda baja por virus respiratorios, con una mortalidad directa del 4%. El 18% de los pac tuvo cistitis hemorrágica por virus BK, con viremia asociada en el 41% de los casos. El 6% de los pacientes presentó falla hematológica asociada a Parvovirus, que un caso fue causa de la pérdida del injerto. Conclusión: las enfermedades virales son una complicación muy frecuente del TCPH y con gran peso en la mortalidad relacionada al trasplante. Los avances terapéuticos han sido menores que los alcanzados en los métodos diagnósticos (AU)

Introduction: Allogeneic hematopietic stem cell transplantation (HSCT) is associated with a slow recovery of the immune system leading to multiple infectious complications. In this study viral infections are evaluated in a retrospective cohort. Material and methods: The data base of the department was reviewed recording viral infections that occurred between 2012-2016. Results: n 215; 91% of the recipients and 70% of the donors were CMV prior to the transplant; 47% of the recipients had a CMV reactivation and 10% developed the disease with a related mortality of 3.1%. Overall, 87% of the recipients and 70% of the donor had a positive serology for EBV and 13% had a reactivation with a viral load of > 20,000 copies/ml. Of the patients, 11% had Herpes zoster, 6% Herpes 6, and 5% Herpes simplex. Adenovirus infection was detected in 25% of the patients, most commonly involving the digestive tract followed by lower respiratory tract infection. Adenovirusrelated mortality was 5.1%. Forty-one acute lower respiratory tract infections due to respiratory viruses were recorded leading to a mortality of 4%. Of all the patients, 18% had BK virus-related hemorrhagic cystitis with associated viremia in 41% of the cases. Six percent of the patients had parvovirusassociated hemotologic failure leading to graft loss in one case. Conclusion: Viral diseases are a very frequent complication in HSCT with a high transplant-related mortality. Advances in therapy have lagged behind advances in diagnostic methods (AU)

Humans , Child, Preschool , Child , Adolescent , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Immunocompromised Host , Prevalence , Virus Diseases/diagnosis , Virus Diseases/epidemiology , Virus Diseases/mortality , Cohort Studies , Retrospective Studies