Current Research in Translational Medicine最新文献

{"title":"DNMT3A-related overgrowth syndrome presenting with immune thrombocytopenic purpura","authors":"Abdullah Sezer ,&nbsp;Öznur Kaya Güneş ,&nbsp;Burçak Kurucu","doi":"10.1016/j.retram.2024.103478","DOIUrl":"10.1016/j.retram.2024.103478","url":null,"abstract":"<div><div>Tatton-Brown-Rahman syndrome (TBRS) is characterized by overgrowth, cognitive deficiency, and distinctive facial features resulting from germline <em>DNMT3A</em> variants. This report describes a four-year-old female diagnosed with TBRS due to a de novo and novel heterozygous <em>DNMT3A</em> variant, NM_022552.5:c.1627G&gt;C:p.(Gly543Arg). Alongside typical TBRS features, she had a history of hospitalization for immune thrombocytopenic purpura (ITP) at five months old. While ITP is clinically diagnosed and has multifactorial origins, studies have demonstrated its autoimmune and genetic components. DNMT3A protein, responsible for DNA methylation, regulates various cellular processes, including hematopoiesis and autoimmunity. It has been reported that ITP patients exhibit decreased expression of <em>DNMT3A</em>, and specific variants linked to decreased platelet counts have been identified in a murine model for TBRS. Additionally, some case reports have been described with multiple cytopenias and thrombocytopenia without hematologic malignancy. In conclusion, this report emphasizes for the first time the occurrence of ITP in a TBRS patient and suggests that autoimmune and hematologic disorders may need to be considered in the follow-up of these patients. However, further evidence is required to establish a direct correlation.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103478"},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR T-cell therapy combined with autologous hematopoietic cell transplantation in patients with refractory/relapsed Burkitt Lymphoma","authors":"Yifan Liu ,&nbsp;Gangfeng Xiao ,&nbsp;Yang Liu ,&nbsp;Sanfang Tu ,&nbsp;Bin Xue ,&nbsp;Yadi Zhong ,&nbsp;Cailu Zhang ,&nbsp;Lili Zhou ,&nbsp;Shiguang Ye ,&nbsp;Yan Lu ,&nbsp;Bing Xiu ,&nbsp;Wenjun Zhang ,&nbsp;Yi Ding ,&nbsp;Jianfei Fu ,&nbsp;Ping Li ,&nbsp;Liang Huang ,&nbsp;Xiu Luo ,&nbsp;Aibin Liang","doi":"10.1016/j.retram.2024.103477","DOIUrl":"10.1016/j.retram.2024.103477","url":null,"abstract":"<div><div>Burkitt lymphoma (BL) is a highly aggressive type of non-Hodgkin lymphomas that have a high likelihood of relapse and are highly refractory to initial treatment. While high-intensity chemotherapy has improved the outcomes, many adult patients still experience treatment failure, and effective salvage therapies are limited. This study retrospectively analyzed the outcomes of 21 relapsed or refractory (R/R) adult BL patients treated with chimeric antigen receptor T-cell (CAR-T) therapy, combined or not with hematopoietic cell transplantation (HCT), across four Chinese hospitals. Patients were grouped based on treatment strategies: autologous HCT followed by CAR T-cell therapy (auto-HCT+CART group, <em>n</em> = 8), and CAR T-cell therapy alone (CART group, <em>n</em> = 13). The auto-HCT+CART group demonstrated superior outcomes, with an overall response rate (ORR) of 87.5 % and significantly higher 1-year overall survival (OS) and progression-free survival (PFS) rates compared to the CART group (<em>p</em> = 0.014 and <em>p</em> = 0.045, respectively). These findings suggest that combining auto-HCT with CAR-T therapy may enhance long-term disease control in R/R BL patients. These encouraging results highlight the need for further prospective studies to validate our data.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103477"},"PeriodicalIF":3.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142551935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico analysis and structural vaccinology prediction of Toxoplasma gondii ROP41 gene via immunoinformatics methods as a vaccine candidate","authors":"Masoumeh Asadi ,&nbsp;Ali Dalir Ghaffari ,&nbsp;Fatemeh Mohammadhasani","doi":"10.1016/j.retram.2024.103475","DOIUrl":"10.1016/j.retram.2024.103475","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Toxoplasma gondii</em> (<em>T. gondii</em>) infects all warm-blooded animals, including humans. Currently, no effective treatments exist to prevent the generation of chronic tissue cysts in infected hosts. Therefore, developing a vaccine to protect to deal with toxoplasmosis is a promising strategy, as a single immunization could provide lifelong protective immunity. Rhoptry proteins (ROPs) play a vital role for the parasite's survival within host cells and perform critical functions during different phases of parasite invasion. Little is known about ROP41 gene. Nevertheless, Understanding the characteristics of ROP41 will enhance diagnostic and vaccine research.</div></div><div><h3>Materials and Methods</h3><div>The current article provides a comprehensive analysis of the essential components of the ROP41 protein, including its transmembrane domain, physico-chemical properties, subcellular location, tertiary and secondary structures, and potential T- and B-cell epitopes. These features were determined by many bioinformatics approaches to identify possible epitopes for developing a highly effective vaccine.</div></div><div><h3>Results</h3><div>ROP41 protein showed 36 possible post-translational modification regions. The ROP41 protein secondary structure contains 17.35 % extended strand, 33.47 % alpha-helix, and 49.18 % random coil. Also, ROP41 showed many possible B- and T-cell epitopes. According to the Ramachandran plot, 90.78 % of amino acid residues had been placed in favored, 3.28 % in outlier, and 5.94 % in allowed areas. Also, the allergenicity and antigenicity evaluation indicated that ROP41 is non-allergenic and immunogenic.</div></div><div><h3>Conclusion</h3><div>The current study offered critical basic and conceptual information on ROP41 to increase a successful vaccine in opposition to continual and acute toxoplasmosis for in addition in vivo assessments. Further research is necessary for the development of vaccines utilizing ROP41 alone or combined with various antigens.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103475"},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect and safety of recombinant human thrombopoietin on haematopoietic reconstitution after allogeneic haematopoietic cell transplantation","authors":"Meilin Tian ,&nbsp;Le Ma ,&nbsp;Jieping Chen ,&nbsp;Qiang Gong","doi":"10.1016/j.retram.2024.103472","DOIUrl":"10.1016/j.retram.2024.103472","url":null,"abstract":"<div><div>Delayed platelet engraftment (DPE) and thrombocytopenia are common complications following myeloablative conditioning in the advanced stage of allogeneic haematopoietic cell transplantation (allo-HCT), and they are associated with transplantation-related mortality and poor prognosis. Therefore, promoting haematopoietic reconstitution after allo-HCT plays a key role in improving patient outcomes. The aim of this retrospective study was to assess the effectiveness and safety of recombinant human thrombopoietin (rhTPO) in promoting haematopoietic reconstruction after allo-HCT. The study included 210 patients who underwent transplantation, with 158 in the rhTPO group and 52 in the control group. Of the total patient population, 120 were males and 90 were females, with a median age of 31 years (range=6 to 59 years). The results showed that the rhTPO group had a median platelet engraftment time that was 14.1 days shorter than that of the control group (14.1 days vs. 21.9 days; <em>P</em> &lt; 0.001). The time for platelet count recovery to 50 × 10^9/L was also shorter in the rhTPO group than in the control group (21.7 days vs. 30.3 days; <em>P</em> &lt; 0.001). Additionally, the granulocyte engraftment time was shorter in the rhTPO group (14.3 days vs. 18.2 days; <em>P</em> &lt; 0.001). There was no significant difference in overall survival (OS) between the rhTPO group and the control group at 2 years after transplantation (77.2% vs. 65.4 %; <em>P</em> = 0.08). Furthermore, there were no significant differences in the amount of platelet transfusions, the rate of platelet engraftment, the rate of DPE, or the incidence of Grade 4 haemorrhage between the groups. Moreover, no adverse reactions were found in the rhTPO group. This study demonstrated that rhTPO administration after allo-HCT effectively reduced the time required for platelet and granulocyte engraftment and was safe.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103472"},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of AML-exosomes on the cellular and molecular properties of bone marrow mesenchymal stromal cells: Expression of JAK/STAT signaling genes","authors":"Maryam Nabigol,&nbsp;Laya Khodayi Hajipirloo,&nbsp;Bentolhoda Kuhestani-dehaghi,&nbsp;Mehdi Allahbakhshian Farsani","doi":"10.1016/j.retram.2024.103474","DOIUrl":"10.1016/j.retram.2024.103474","url":null,"abstract":"<div><h3>Purpose of study</h3><div>Despite the various therapeutic options introduced for AML treatment, therapy resistance and relapse are still the main obstacles. It is well known that alterations in the bone marrow microenvironment (BMM) play a crucial role in leukemia growth and the treatment failure of AML. Evidence shows that exosomes alter the components of BMM in a way that support leukemia survival, leading to chemoresistance. In this study, we evaluated the effect of AML exosomes on the biological functions of human bone marrow mesenchymal stromal cells (h BM-MSCs), especially alteration in the expression of the JAK/STAT signaling genes, as a leukemia-favoring pathway.</div></div><div><h3>Method</h3><div>Exosomes were isolated from the HL-60 cell line and characterized using flow cytometry, Transmission Electron Microscopy (TEM), and Dynamic Light Scattering (DLS) technique. The exosome protein content was assessed using a bicinchoninic acid (BCA) protein assay kit in order to determine the concentration of exosomes. Subsequently, MSCs were treated with varying concentrations of AML exosomes, and data was obtained using MTT, cell cycle, apoptosis, and ki67 assays. Additionally, gene expression analysis was conducted through qRT-PCR.</div></div><div><h3>Result</h3><div>AML exosomes regulated the viability and survival of MSCs in a concentration-dependent manner. The qRT-PCR data revealed that treatment with AML exosomes at a concentration of 50 μg/mL led to a significant upregulation of JAK2, STAT3, and STAT5 genes in MSCs.</div></div><div><h3>Conclusion</h3><div>Because the JAK/STAT signaling pathway has been shown to play a role in the proliferation and survival of leukemic cells, our results suggest that AML exosomes stimulate MSCs to activate this pathway. This activation may impede AML cell apoptosis, potentially leading to chemoresistance and relapse.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103474"},"PeriodicalIF":3.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transplantation effect of pegylated granulocyte colony-stimulating factor mobilized hematopoietic stem cells may be superior to that of G-CSF mobilized hematopoietic stem cells in haploidentical allogeneic hematopoietic cell transplantation","authors":"Junjie Cao ,&nbsp;Xianxu Zhuang ,&nbsp;Renzhi Pei ,&nbsp;Ying Lu ,&nbsp;Peipei Ye ,&nbsp;Dong Chen ,&nbsp;Xiaohong Du ,&nbsp;Shuangyue Li ,&nbsp;Xuhui Liu","doi":"10.1016/j.retram.2024.103473","DOIUrl":"10.1016/j.retram.2024.103473","url":null,"abstract":"<div><div>Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells have become the preferred source of hematopoietic stem cells. We compared the effectiveness of G-CSF and pegylated G-CSF (peg-G-CSF) for hematopoietic stem cell mobilization in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) donors, and evaluated the transplant outcomes. We conducted a matched retrospective cohort study. Donors mobilized with peg-G-CSF (<em>n</em> = 70) and G-CSF (<em>n</em> = 70). 140 consecutive patients diagnosed with acute leukemia who underwent haplo-HSCT were included in this study. The findings revealed that the peg-G-CSF cohort exhibited significantly elevated myeloid-derived suppressor cells (MDSCs) levels in their grafts when compared to the G-CSF cohort (<em>P</em> &lt; 0.001). The 100-day cumulative incidence (CI) of grade III-IV acute graft-versus-host disease (GVHD) and 1-year CI of moderate-to-severe chronic GVHD were 4.3% vs 14.3 % (<em>P</em> = 0.047) and 11.2% vs 27.4 % (<em>P</em> = 0.023), in the peg-G-CSF group and G-CSF group. Patients reveiving mobilized stem cell with peg-G-CSF had a significantly greater likelihood of 1-year GVHD-free relapse-free survival (GRFS) compared to patients reveiving mobilized stem cell with G-CSF (74.9% vs 37.9 %, <em>P</em> &lt; 0.001). The higher graft MDSCs proportion was associated with lower grade II-IV aGVHD, cGVHD (<em>P</em> &lt; 0.05) and higher GRFS in the univariate analysis (<em>P</em> &lt; 0.05). Multivariate analysis showed that MDSCs proportion higher than 11.36 % (HR, 0.305; 95 % CI, 0.154–0.606; <em>P</em> = 0.001) and peg-G-CSF for stem cell mobilization (HR, 0.466; 95 % CI, 0.251–0.865; <em>P</em> = 0.016) were independent prognostic factors of GRFS. The superior survival rates observed in recipients of peg-G-CSF-mobilized cells are likely due to reduced acute GVHD, potentially mediated by the increased MDSCs within the grafts.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"72 4","pages":"Article 103473"},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point of care CD19 chimeric antigen receptor (CAR) T-cells for relapsed/refractory acute myeloid leukemia (AML) with aberrant CD19 antigen expression","authors":"Ivetta Danylesko ,&nbsp;Noga Shem-Tov ,&nbsp;Ronit Yerushalmi ,&nbsp;Elad Jacoby ,&nbsp;Amos Toren ,&nbsp;Roni Shouval ,&nbsp;Orit Itzhaki ,&nbsp;Abraham Avigdor ,&nbsp;Avichai Shimoni ,&nbsp;Arnon Nagler","doi":"10.1016/j.retram.2024.103471","DOIUrl":"10.1016/j.retram.2024.103471","url":null,"abstract":"<div><div>Relapsed/refractory (r/r) acute myeloid leukemia (AML) is associated with poor prognosis. CD19 is a B-cell marker, is aberrantly expressed in AML, mostly with t(8; 21)(q22; q22.1). Here we report the results of a phase 2 study giving point of care produced CD19 CAR T- cells for r/r AML with aberrant expression of CD19 (NCT04257175). Lymphodepletion included fludarabine and cyclophosphamide The response was evaluated by bone marrow (BM) aspiration on day 28. Six patients (5 adults and 1 child) were included. Median number of previous chemotherapy lines was 4 (range, 3–8) and four patients received CAR T-cells 8–18 months post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cytokine release syndrome (CRS) of any grade occurred in all patients, and 1 patient had grade 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 patients at low grades. Tocilizumab was administered to 2 patients and corticosteroids to 3 patients. Four patients achieved a complete remission (CR), while 2/6 progressed (PD). Three patients (2 with CR and 1 with PD) underwent allo-HSCT (it was the second transplant in 2) 2–5 months post CAR T-cells infusion. The median duration of response in patients achieving CR was 8.5 (range; 3–14) months. However, all patients eventually died within 5 (1–18) months.</div><div>In conclusion, CD19 CAR T- cell treatment for AML is feasible and safe. However, the response is short and should be followed by allo-HSCT. Hopefully, future long term results will be improved by combining the CAR T- cell therapy with the emerging novel effective anti-leukemic compounds.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"72 4","pages":"Article 103471"},"PeriodicalIF":3.2,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired survival of patients with non donor-specific anti-HLA antibodies before HLA-mismatched allogeneic stem cell transplantation","authors":"Antonio Milano ,&nbsp;Giuliana Lando ,&nbsp;Giulia Di Maggio ,&nbsp;Giorgia Cornacchini ,&nbsp;Giovanni Grillo ,&nbsp;Roberto Cairoli ,&nbsp;Silvano Rossini ,&nbsp;Roberto Crocchiolo","doi":"10.1016/j.retram.2024.103464","DOIUrl":"10.1016/j.retram.2024.103464","url":null,"abstract":"<div><h3>Background</h3><p>While the detrimental role of donor-specific anti-HLA antibodies (DSAs) is well-described in the setting of hematopoietic stem cell transplantation (HSCT), few studies focus on non donor-specific ones and with controversial results.</p></div><div><h3>Methods</h3><p>We here report our monocenter experience on 64 adult patients receiving allogeneic HSCT from a HLA-mismatched donor between 2014 and 2022 who were tested for the presence of anti-HLA antibodies before transplant, focusing on fifteen patients with non donor-specific anti-HLA antibodies.</p></div><div><h3>Results</h3><p>The survival of patients with non donor-specific anti-HLA antibodies was inferior with respect to patients without anti-HLA antibodies and similar to patients with DSAs. Median survival of patients with non donor-specific anti-HLA antibodies was 21 months (95 % CI: 9–42) vs. 61 months (95 % CI: 17–77) among the anti-HLA antibody-negative patients, with a significantly higher mortality incidence rate ratio (3.3 times-fold greater, <em>p</em> = 0.01). No pattern of death causes was found</p></div><div><h3>Conclusions</h3><p>In this monocenter series of HLA-mismatched HSCTs, impaired survival was observed in adult patients having non donor-specific anti-HLA antibodies before transplant, similar to those with DSAs. Our findings support those antibodies as a negative predictive factor even if they are not directed against the donor, thus warranting further investigation on larger cohorts.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"72 3","pages":"Article 103464"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of co-transplantation of umbilical cord blood and third-party mesenchymal stromal cells after (non)myeloablative conditioning in patients with hematological malignancies","authors":"Simon Planken ,&nbsp;Ann De Becker ,&nbsp;Tessa Kerre ,&nbsp;Hélène Schoemans ,&nbsp;Frédéric Baron ,&nbsp;Carlos Graux ,&nbsp;Ivan Van Riet ,&nbsp;Chantal Lechanteur ,&nbsp;Etienne Baudoux ,&nbsp;Rik Schots ,&nbsp;Yves Beguin ,&nbsp;Transplant Committee of the Belgian Hematology Society.","doi":"10.1016/j.retram.2024.103466","DOIUrl":"10.1016/j.retram.2024.103466","url":null,"abstract":"<div><p>Umbilical cord blood (UCB) is an alternative source of stem cells for patients lacking a 9/10 or 10/10 HLA identical donor. However, after UCB transplantation, time to engraftment and immune recovery are prolonged, increasing the risk of fatal complications. Mesenchymal stromal cells (MSC) can support hematopoietic engraftment and have immunosuppressive effects.</p><p>The primary objective of this phase I/II multicenter study was to determine the feasibility and safety of UCB transplantation with co-infusion of third party MSC, as assessed by treatment related mortality (TRM) at day 100. Secondary objectives were engraftment, immune recovery, occurrence of graft versus host disease (GVHD), infections, disease free survival, relapse incidence and overall survival.</p><p>Eleven patients were grafted according to this protocol. Allogeneic transplantation after co-infusion appears feasible with 18 % TRM at day 100. Engraftment data show a median time of 16 days to neutrophil and 27 days to platelet recovery, which is shorter than what is usually reported after UCB transplantation. Only 1 episode of acute GVHD was reported.</p><p>In conclusion, MSC and UCB co-transplantation is feasible and might help overcome some of the drawbacks of UCB transplantation.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"72 4","pages":"Article 103466"},"PeriodicalIF":3.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective red blood cell depletion by apheresis in sheep causes severe normovolemic anemia","authors":"Anna-Lena Semmler ,&nbsp;Jan-Philipp Köhler ,&nbsp;Lara Regolien ,&nbsp;Franziska Bayer ,&nbsp;Nikolay Polyansky ,&nbsp;Elise Gradhand ,&nbsp;Andreas von Knethen ,&nbsp;Kai Zacharowski ,&nbsp;Fabian Nocke ,&nbsp;Katja B. Ferenz ,&nbsp;Joachim Schwäble ,&nbsp;Halvard Bonig ,&nbsp;Eva Herrmann ,&nbsp;Isabelle Hornung ,&nbsp;Andrea U. Steinbicker","doi":"10.1016/j.retram.2024.103463","DOIUrl":"10.1016/j.retram.2024.103463","url":null,"abstract":"<div><h3>Background</h3><p>: The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4–6 g dL⁻¹ using apheresis in sheep.</p></div><div><h3>Methods</h3><p>: <em>In vitro</em> experiments were performed first to establish the apheresis protocol. <em>In vivo</em>, anesthetized ewes underwent a sham protocol without apheresis (<em>n</em> = 5) or apheresis (<em>n</em> = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired <em>t</em>-test with Welch`s correction was used.</p></div><div><h3>Results</h3><p>: Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL⁻¹ in the apheresis group compared to 9.1 g dL⁻¹ in sham (*<em>p</em> &lt; 0.0001). Hct (11.2% vs 25.1 %, *<em>p</em> = 0.01) and RBCs (3.7 vs 8.2 × 10⁶/µl, *<em>p</em> = 0.003) also decreased. The relative number of platelets compared to baseline was different (55.6 ± 10.6% vs. 100 ± 0 %, *<em>p</em> = 0.004), but no hemorrhage was observed. White blood cells (WBCs), lactate, prothrombin ratio and activated partial thromboplastin time (aPTT) remained within similar ranges.</p></div><div><h3>Conclusions</h3><p>: Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"72 4","pages":"Article 103463"},"PeriodicalIF":3.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}