Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations

Immature hematopoietic progenitors are a constant source for renewal of hemocyte populations and the basic component of the tissue and cell repair apparatus. A unique property of these cells of internalizing extracellular double-stranded DNA has been previously shown. The leukostimulatory effect demonstrated in our pioneering studies was considered to be due to the feature of this cell. In the present research, we have analyzed the effects of DNA genome reconstructor preparation (DNAgr), DNAmix, and human recombinant angiogenin on both hematopoietic stem cells and multipotent progenitors. Treatment with bone marrow cells of experimental mice with these preparations stimulates colony formation by hematopoietic stem cells and proliferation of multipotent descendants. The main lineage responsible for this is the granulocyte-macrophage hematopoietic lineage. Using fluorescent microscopy as well as FACS assay, co-localization of primitive c-Kit- and Sca-1-positive progenitors and the TAMRA-labeled double-stranded DNA has been shown. Human recombinant angiogenin was used as a reference agent. Cells with specific markers were quantified in intact bone marrow and colonies grown in the presence of inducers. Quantitative analysis revealed that a total of 14,000 fragment copies of 500 bp, which is 0.2% of the haploid genome, can be delivered into early progenitors. Extracellular double-stranded DNA fragments stimulated the colony formation in early hematopoietic progenitors from the bone marrow, which assumed their effect on cells in G0. The observed number of Sca1+/c-Kit+ cells in colonies testifies to the possibility of both symmetrical and asymmetrical division of the initial hematopoietic stem cell and its progeny.

Common mental disorders in hematopoietic stem cell transplant patients: a scoping review / Trastornos mentales comunes en pacientes con trasplante de células madre hematopoyéticas: revisión del alcance / Transtornos mentais comuns em pacientes transplantados com células-tronco hematopoéticas: revisão de escopo

ABSTRACT Objective: to map common recurrent mental disorders in patients undergoing hematopoietic stem cell transplantation. Methods: this is a scoping review carried out in January 2022 in electronic databases and repositories of dissertations and thesis. Studies that answered the research question, met the objective of the study and were available in full electronically, in any language, were included. Results: the sample consisted of 28 studies, 14 of which were published in the United States of America. The common mental disorders found were depressive, anxiety, post-traumatic stress and mood disorders. Twenty symptoms were mentioned, among the most prevalent are fatigue and sleep disorders/insomnia. Conclusions: the difficulty and importance of carrying out the differential diagnosis of these disorders were highlighted, since their symptoms can be confused with other health problems and have a strong potential to interfere with patients' evolution.

RESUMEN Objetivo: mapear los trastornos mentales recurrentes comunes en pacientes sometidos a trasplante de células madre hematopoyéticas. Métodos: se trata de una revisión de alcance realizada en enero de 2022 en bases de datos electrónicas y repositorios de disertaciones y tesis. Se incluyeron publicaciones que respondieron a la pregunta de investigación, cumplieron con el objetivo del estudio y estaban disponibles en su totalidad en formato electrónico, en cualquier idioma. Resultados: la muestra estuvo compuesta por 28 estudios, 14 de los cuales fueron publicados en los Estados Unidos de América. Los trastornos mentales comunes encontrados fueron depresión, ansiedad, estrés postraumático y trastornos del estado de ánimo. Se mencionaron 20 síntomas, entre los más prevalentes se encuentran fatiga y trastornos del sueño/insomnio. Conclusiones: se destacó la dificultad e importancia de realizar el diagnóstico diferencial de estos trastornos, ya que sus síntomas pueden confundirse con otros problemas de salud y tienen un fuerte potencial de interferir en la evolución del paciente.

RESUMO Objetivo: mapear os transtornos mentais comuns recorrentes em pacientes submetidos ao transplante de células-tronco hematopoéticas. Métodos: trata-se de revisão de escopo realizada em janeiro de 2022 em bases de dados eletrônicas e repositórios de dissertações e tese. Foram incluídas publicações que respondessem à questão de pesquisa, atendessem ao objetivo do estudo e que estivessem disponíveis na íntegra em meio eletrônico, em qualquer idioma. Resultados: a amostra foi composta por 28 estudos, dos quais 14 foram publicados nos Estados Unidos da América. Os transtornos mentais comuns encontrados foram os transtornos depressivos, de ansiedade, estresse pós-traumático e de humor. Foram citados 20 sintomas, entre os mais prevalentes estão a fadiga e distúrbios do sono/insônia. Conclusões: evidenciaram-se a dificuldade e a importância de realizar o diagnóstico diferencial desses transtornos, uma vez que seus sintomas podem ser confundidos com outros problemas de saúde e têm forte potencial para interferir na evolução do paciente.

Research progress on the mechanism of bone marrow suppression after chemotherapy / 国际肿瘤学杂志

As an effective treatment for cancer, chemotherapy not only removes tumor cells, but also produces obvious killing effects on proliferating cells, especially hematopoietic cells, resulting in bone marrow suppression after chemotherapy, and affecting the effects of chemotherapy drug treatment and treatment cycle. Therefore, starting from the aspects of hematopoietic microenvironment damage and hematopoietic stem cell aging, to explore the mechanism of myelosuppression after chemotherapy, which provides new ideas and theoretical support for the intervention and management of bone marrow suppression after cancer chemotherapy.

Trasplante alogénico en leucemia mieloide aguda y la importancia genética en desarrollo de nuevos tratamientos / Allological transplant in acute myeloid leukemia, the genetic importance for the development of new treatments

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.

SARS-COV-2 screening in allogeneic hematopoietic stem cell donors: Implications for the evaluation process and eligibility

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.

Using informational questionnaires to turn blood donors into hematopoietic stem cell voluntary donors: a randomized controlled trial / 中国输血杂志

【Objective】 To explore effective ways to mobilize more blood donors to become voluntary donors of hematopoietic stem cells (HSCs), so as to increase the HSCs supply in China. 【Methods】 Two scales(the information scale and the control scale) with the same items were designed and both included questions concerning the knowledge of HSCs donation and the level of demand. The information scale indicated the correct answer to these questions, while the control scale did not. A total of 3 000 blood donors in Guangzhou were randomly assigned into the intervention group (n=1 500, filled in the information scale) and the control group (n=1 500, filled in the control scale). 【Results】 Blood donors who filled in the informational scale expressed a higher intention to become HSCs volunteers (MInformation =4.32, SD=0.87; MControl=4.02, SD=0.93, t(529)=3.87, P<0.001). Altruism and perceived need (the degree of HSCs demands) were the moderators of grouping and intention, that is, the information scale made blood donors, with stronger altruism and higher perceived need, more willing to become stem cell volunteers. Perceived risk (the negative impact of HSCs donation on health) was a partial mediator of grouping and intention. The information scale reduced blood donors' anxiety about the risk of HSCs donation, and promoted their intention to become HSCs volunteers. 【Conclusion】 This study proved that the informational scale can effectively mobilize blood donors to become HSCs volunteers.

Aging-elevated inflammation promotes DNMT3A R878H-driven clonal hematopoiesis

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.

Research status and progress of acute myeloid leukemia stem cells / 中国基层医药

Acute myeloid leukemia is a clonal malignant proliferative disease of myeloid blasts of the hematopoietic system. The leukemia cell population is composed of cells of different stages. Acute myeloid leukemia stem cells are the cells that may cause diseases in immunodeficient animals and can regenerate themselves through continuous transplantation, which causes leukemia. Since more than 96% of leukemia stem cells are in the G0 stage, they may escape the effects of chemical drug stabbing, leading to drug resistance and recurrence of leukemia. Therefore, the key to the treatment of acute myeloid leukemia has always been how to remove leukemia stem cells without damaging hematopoietic stem cells. This review paper addresses the new developments in the immunophenotype of leukemia stem cells and leukemia stem cells-targeting therapy for acute myeloid leukemia.

Advances in the understanding of clonal hematopoiesis in cardiovascular disease / 中华老年医学杂志

Cardiovascular disease is a leading cause of death among the elderly and the incidence of coronary artery disease progressively increases with advancing age.Traditional risk factors are incompletely predictive of cardiovascular disease development.With the advent of high-throughput next-generation genome sequencing technologies in recent years, some studies have indicated that aging is associated with an increased frequency of somatic mutations of hematological neoplasm-related genes in the hematopoietic system, providing a competitive growth advantage for mutant hematopoietic cells and thus allowing for their clonal expansion, a phenomenon known as clonal hematopoiesis of indeterminate potential(CHIP). CHIP is common in middle-aged and elderly populations and is associated with increased risks of hematological cancer and all-cause death.There is growing evidence that CHIP is involved in the development and progression of multiple cardiovascular disorders through the activation of inflammatory responses.In this review, we will give an overview of current advances in the understanding of clonal hematopoiesis in cardiovascular disease.

Biochemical and histopathological evaluations of chronic renal failure rats treated with pluripotent human stem cells

Abstract Regeneration of damaged kidney cells using stem cells is the current research approach in the treatment of chronic renal failure (CRF). In the present study, the histopathological and biochemical techniques were used to evaluate stem cells' (SCs) role in treatment of CRF. Sixty-four rats were divided into eight groups. Group I (GI): rats were injected with doxorubicin (15 mg/kg) to initiate CRF. GII-GVII: rats were injected with doxorubicin and treated with SCs (1x106 MSCs or/and 2x104 HSCs/rat) with/without growth factors extract (200 µL/rat) and/or immunosuppressor (cyclosporine A, 5 mg/kg/day). GVIII: rats treated with PBS (100 µL/kg/day). Levels of creatinine, urea and uric acid were increased in rats sera after injection with doxorubicin, while blood electrolyte levels of Na, K, P and Mg were decreased. Also, histopathological abnormalities such as hyalinized blood vessels, degenerated hyalinized glomerulus tubules and cell debris in the lumen and degeneration of renal tissues were observed in these rats. After treatment with SCs, all these parameters restore their normal values with regeneration of the damaged cells as demonstrated in histopathology of the treated groups. It can be concluded that, the use of SCs in treatment of kidney diseases is a promising approach and needs more efforts.

Proteção ineficaz em pacientes submetidos ao transplante de células-tronco hematopoiéticas: análise de conceito / Ineffective protection in patients undergoing hematopoietic stem cell transplantation: concept analysis

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.

Histone Deacetylase Inhibitors in the in Vitro Expansion of Hematopoietic Stem Cells / 中国医学科学院学报

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.

Progress of the mechanism of Wnt signaling pathway in T-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

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.

Muscle mass evaluation and influencing factors of sarcopenia in allogeneic hematopoietic stem cell transplantation patients / 中国组织工程研究

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.

Culture and application of thymic organoids: a review / 生物工程学报

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.

Effect observation of different collection procedures of blood cell separator on collection of autologous peripheral blood hematopoietic stem cells in children / 白血病·淋巴瘤

Objective:To investigate the effect of different collection procedures of COBE Spectra blood cell separator on collection of autologous peripheral blood hematopoietic stem cells in children.Methods:The clinical data of 10 children who were collected autologous peripheral blood hematopoietic stem cells with the monocytes (MNC) or fully automatic peripheral blood stem cells (AutoPBSC) programs of COBE Spectra blood cell separator in the Children's Hospital of Soochow University from July 2018 to January 2020 were retrospectively analyzed, and the children were 3-10 years old with the body weight of 15-31kg. There were 5 cases in MNC group and 5 cases in AutoPBSC group.Results:Autologous peripheral blood hematopoietic stem cells were collected for 25 times, with an average of 2.5 times (1-4 times), 10 times in MNC group and 15 times in AutoPBSC group. The number of stem cells [the median (the range)] before collection was 19.3/μl (3.5-129.0/μl) in MNC group and 9.4/μl (2.2-38.7/μl) in AutoPBSC group. The number of CD34 + cells of single collection was 1.22×10 6/kg (0.18×10 6/kg-6.30×10 6/kg) in MCN group and 0.85×10 6/kg (0.13×10 6/kg-2.64×10 6/kg) in AutoPBSC group. Correlation analysis showed that there was a positive correlation between the number of collected CD34 + cells and the number of stem cells before collection (AutoPBSC group: r=0.921, P < 0.01; MNC group: r=0.833, P=0.003). The collection efficiency was 5.4% (3.4%-11.2%) in MNC group and 10.4% (4.7%-13.9%) in AutoPBSC group, and the difference was statistically significant ( Z=2.163, P = 0.031). Conclusion:The collection effect of children's autologous peripheral blood hematopoietic stem cells with COBE Spectra blood cell separator AutoPBSC program is better than that with MNC program.

Mesenchymal stromal cells represent a therapeutic option for systemic sclerosis patients / Células estromales mesenquimales representan una opción terapéutica en pacientes con esclerosis sistémica

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.

Mechanism of angelica polysaccharide regulating mitochondrial apoptosis for improving bone marrow failure / 中国组织工程研究

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.

Evaluation of nutritional risk factors in hematopoietic stem cell transplantation-eligible patients / Avaliação dos fatores de riscos nutricionais em pacientes pré-transplante de célula-tronco hematopoiética

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.

The impact of multiple myeloma induction therapy on hematopoietic stem cell mobilization and collection: 25-year experience

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.