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.

Five different vascular accesses on the outcome in peripheral blood stem cells collection: a network Meta-analysis / 中国实用护理杂志

Objective:To analyze the effect of different vascular access on the outcome in peripheral blood stem cells collection by a network Meta-analysis, and to provide a reference for clinical medical staff to select the best vascular access.Methods:A systematic search was carried out in Chinese Knowledge Infrastructure database (CNKI), Wanfang Database, VIP Database, Chinese Biomedical Literature Database, Cochrane Library, Web of Science, PubMed, Embase, from inception until April 15, 2023. Two researchers independently screened literature and extracted data. Bayesian network meta-analysis was performed using R4.2.2 and Addis-1.16.6 softwares.Results:A total 7 pieces of research were included, 5 vascular access methods were peripheral artery, peripheral vein, artery-vein, femoral vein-central venous catheter (FV-CVC), and internal jugular vein-CVC (IJV-CVC). The results showed that compared with the peripheral veins, there was no significant difference on CD34 cells between other vascular accesses in the primary outcome measure when collected peripheral blood stem cell collection. On the single blood volume treatment time, peripheral vein and IJV-CVC were statistically significant ( MD = 14.80, 95% CI 2.70-22.38, P<0.05) . The SUCRA ranking probability chart showed that on CD34 cells, FV- CVC>IJV-CVC>artery-vein>peripheral artery>peripheral vein access; for a single blood volume treatment time and monocyte number, peripheral artery was superior and the next was peripheral vein. Conclusions:Current evidence suggested that Peripheral artery may be the best vascular access in peripheral blood stem cells collection, which opens a new way to establish the vascular access for peripheral blood stem cells collection, but it needs to be confirmed by large clinic trials.

Lipopolysaccharide induces aging phenotype of hematopoietic stem cells in bone marrow and spleen of young mice / 中国病理生理杂志

AIM:This study aim to investigate the effects of lipopolysaccharide(LPS)-induced inflammation on the aging phenotype of hematopoietic stem/progenitor cells(HSPCs)in the bone marrow(BM)and spleen of mice.METHODS:(1)Young(2-month old)wild-type(WT)mice were treated with LPS to establish an actue inflammation model.The percentage of HSPCs in the BM and spleen of mice after LPS stimulation,as well as the ratio of mature cells in peripheral blood(PB)and spleen,were analyzed using flow cytometry.The proliferation of HSPCs in the BM and spleen was evaluated by examining the expression of the proliferation marker Ki67.In addition,changes in CD45 expression on HSPCs in the spleen of mice following LPS exposure were investigated by flow cytometry.(2)The percentage of HSPCs in BM and mature cells in PB and spleen of both young(2-month old)and old(24-month old)WT mice were analyzed by flow cytometry.(3)The transcriptome changes of hematopoietic stem cells(HSCs)after LPS stimulation was performed by an in silico analysis.RESULTS:(1)Mice exposed to LPS exhibited a significant increase in the percentage of HSPCs in BM and a marked elevation in the percentages of myeloid cells in PB and spleen compared to the mice in control group(P<0.05).(2)LPS exposure resulted in increased spleen weight and cell counts(P<0.05),along with a higher per-centage of HSPCs in the spleen compared to controls(P<0.05).(3)LPS stimulation promoted the proliferation of HSPCs in the BM and spleen(P<0.05).(4)The expression of CD45 was reduced on HSPCs from spleen of mice after LPS stimu-lation(P<0.01).(5)In comparison to young mice,aged mice showed an increase in spleen weight and a higher percent-age of HSPCs in the spleen(P<0.05).(6)Aged mice,in comparison to young mice,demonstrated a significantly higher percentage of HSPCs in the BM and myeloid skewing in the PB and spleen(P<0.01).(7)The silico analysis revealed up-regualtion of reactive oxygen species(ROS)and apoptosis signaling in HSPCs following LPS stimulation.CONCLU-SION:Young HSPCs stimulated by LPS exhibited an increase in cell number,a bias towards myeloid differentiation,en-hanced extramedullary hematopoiesis,and elevated levels of ROS and apoptosis,all of which collectively manifested the aging phenotype of HSPCs.

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.

Research progress on heterogeneity of bone marrow mesenchymal stem cell populations related to hematopoietic system radiation injury repairing / 军事医学

Efficient treatment of hematopoietic system radiation injuries that occur in medical and military settings is a real problem that has attracted increasing attention.However,current treatments for hematopoietic system radiation injury are lacking.Mesenchymal stem cells(MSCs)are one of the important components of the bone marrow microenvironment.The role of infusion of exogenous MSCs or their exosomes in promoting hematopoietic system radiation damage repair has been extensively reported.However,there have been relatively few studies on the responses of MSCs in situ in bone marrow after radiation injury.This review focuses on the in situ bone marrow MSC populations that are potentially involved in hematopoietic system radiation injury repair and on the heterogeneity of these MSCs.

Research Advances on Strategies to Promote Homing and Engraftment of Hematopoietic Stem Cells--Review / 中国实验血液学杂志

The homing and engraftment of hematopoietic stem cells (HSC) into bone marrow is the first critical step for successful clinical hematopoietic stem cell transplantation (HSCT). SDF-1 / CXCR4 is considered to be a very promising target to promote HSC homing. In recent years, with the in-depth research on the HSC homing, a variety of new strategies for promoting HSC homing and engraftment have been explored, such as nuclear hormone receptor, histone deacetylase inhibitor, prostaglandin and metabolic regulation, so as to increase the success rate of HSCT and improve the survival of patients. In this review, the recent research advances in the mechanism of HSC homing and strategies to promote HSC homing and engraftment were summarized and discussed.

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.

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.