Phase I Study of Intravitreal Injection of Autologous CD34+ Stem Cells from Bone Marrow in Eyes with Vision Loss from Retinitis Pigmentosa.

Purpose: To evaluate the feasibility and safety of intravitreal injection of autologous CD34+ stem cells from bone marrow (BMSCs) in eyes with vision loss from retinitis pigmentosa (RP). Design: Phase I prospective, open-label, single-center study. Participants: Seven eyes (7 patients) with RP with best-corrected visual acuity (BCVA) of 20/60 to 20/400 or visual field constriction to within 10°. Methods: A comprehensive examination with ETDRS BCVA, macular OCT, perimetry, and fluorescein angiography was performed at baseline, 1 to 3 months, and 6 months after study treatment. Bone marrow aspiration, isolation of CD34+ BMSCs under good manufacturing practice conditions, and intravitreal cell injection were performed on the same day. The CD34+ cells were isolated from bone marrow using a Ficoll gradient and the Miltenyi CliniMACS system. Isolated CD34+ cells were released for clinical use if viability, sterility, and purity met the release criteria accepted by the United States Food and Drug Administration for this clinical study. Main Outcome Measures: Number of CD34+ cells isolated for injection and adverse events associated with study treatment during follow-up. Secondary outcome measures are changes in BCVA and perimetry. Results: All isolated CD34+ cells passed the release criteria. A mean of 3.26 ± 0.66 million viable CD34+ cells (range 1.6 to 7.05 million) were injected intravitreally per eye. No adverse event was noted during the study follow-up except for 1 participant who was noted with transient cells in the anterior chamber with mild elevation in intraocular pressure at 18 hours after study injection which normalized by 24 hours. Best-corrected visual acuity remained within 2 lines of baseline or improved in all participants at 6 months follow-up. Perimetry was stable or improved in all eyes during study follow-up except 1 eye with transient improvement at 1 month and worsening of both eyes at 6 months. Conclusions: Intravitreal injection of autologous CD34+ BMSCs is feasible and appears to be well tolerated in eyes with vision loss from RP. A larger randomized prospective study would be needed to evaluate further the safety and potential efficacy of this cell therapy for vision loss associated with RP. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Wenshen Xiaozheng Tang alleviates fibrosis in endometriosis by regulating differentiation and paracrine signaling of endometrium-derived mesenchymal stem cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Wenshen Xiaozheng Tang (WXT), a traditional Chinese medicine (TCM) decoction, is effective for treating endometriosis. However, the effect of WXT on endometrium-derived mesenchymal stem cells (eMSCs) which play a key role in the fibrogenesis of endometriosis requires further elucidation. AIMS OF THE STUDY: The aim of this study was to clarify the potential mechanism of WXT in improving fibrosis in endometriosis by investigating the regulation of WXT on differentiation and paracrine of eMSCs. MATERIALS AND METHODS: The nude mice with endometriosis were randomly divided into model group, WXT group and mifepristone group. After 21 days of treatment, the lesion volume was calculated. Fibrosis in the lesions was evaluated by Masson staining and expression of fibrotic proteins. The differentiation of eMSCs in vivo was explored using a fate-tracking experiment. To further clarify the regulation of WXT on eMSCs, primary eMSCs from the ectopic lesions of endometriosis patients were isolated and characterized. The effect of WXT on the proliferation and differentiation of ectopic eMSCs was examined. To evaluate the role of WXT on the paracrine activity of ectopic eMSCs, the conditioned medium (CM) from ectopic eMSCs pretreated with WXT was collected and applied to treat ectopic endometrial stromal cells (ESCs), after which the expression of fibrotic proteins in ectopic ESCs was assessed. In addition, transcriptome sequencing was used to investigate the regulatory mechanism of WXT on ectopic eMSCs, and western blot and ELISA were employed to determine the key mediator. RESULTS: WXT impeded the growth of ectopic lesions in nude mice with endometriosis and reduced collagen deposition and the expression of fibrotic proteins fibronectin, collagen I, α-SMA and CTGF in the endometriotic lesions. The fate-tracking experiment showed that WXT prevented human eMSCs from differentiating into myofibroblasts in the nude mice. We successfully isolated eMSCs from the lesions of patients with endometriosis and demonstrated that WXT suppressed proliferation and myofibroblast differentiation of ectopic eMSCs. Moreover, the expression of α-SMA, collagen I, fibronectin and CTGF in ectopic ESCs was significantly down-regulated by the CM of ectopic MSCs pretreated with WXT. Combining the results of RNA sequencing, western blot and ELISA, we found that WXT not only reduced thrombospondin 4 expression in ectopic eMSCs, but also decreased thrombospondin 4 secretion from ectopic eMSCs. Thrombospondin 4 concentration-dependently upregulated the expression of collagen I, fibronectin, α-SMA and CTGF in ectopic ESCs, indicating that thrombospondin 4 was a key mediator of WXT in inhibiting the fibrotic process in endometriosis. CONCLUSION: WXT improved fibrosis in endometriosis by regulating differentiation and paracrine signaling of eMSCs. Thrombospondin 4, whose release from ectopic eMSCs is inhibited by WXT, may be a potential target for the treatment of endometriosis.

Advances in meniscus tissue engineering: Towards bridging the gaps from bench to bedside.

Meniscus is vital for maintaining the anatomical and functional integrity of knee. Injuries to meniscus, commonly caused by trauma or degenerative processes, can result in knee joint dysfunction and secondary osteoarthritis, while current conservative and surgical interventions for meniscus injuries bear suboptimal outcomes. In the past decade, there has been a significant focus on advancing meniscus tissue engineering, encompassing isolated scaffold strategies, biological augmentation, physical stimulus, and meniscus organoids, to improve the prognosis of meniscus injuries. Despite noteworthy promising preclinical results, translational gaps and inconsistencies in the therapeutic efficiency between preclinical and clinical studies exist. This review comprehensively outlines the developments in meniscus tissue engineering over the past decade (Scheme 1). Reasons for the discordant results between preclinical and clinical trials, as well as potential strategies to expedite the translation of bench-to-bedside approaches are analyzed and discussed.

Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells.

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.

[Caregiving Experience With a Young Father With Multiple Myeloma Undergoing Renal Dialysis and Autologous Stem Cell Transplantation].

This case report addresses the author's experience providing nursing care to a 37-year-old patient diagnosed with multiple myeloma requiring regular renal dialysis due to disease progression who received autologous stem cell transplantation. The patient was diagnosed with cancer in young adulthood and, as a father figure, faced various psychological issues associated with the unexpected challenges encountered during their treatment phase. Psychosocial health, which is closely associated with quality of life in patients with cancer, has gained increasing attention in recent years. The limited research published on the subject of fathers diagnosed with cancer encouraged the author to detail her experience with this case. The care period was from August 5th to August 19th, 2022. During the care period, the Gordons's 11 functional health assessment was applied, with potentially severe infections, coping disorders, anxiety, potential risk of injury existing or potential nutritional deficiencies, oral mucosal changes, and diarrhea identified as the primary health problems of concern. Nursing interventions applied included providing protective isolation measures to prevent post-transplant infection, helping the patient learn effective ways to cope with emotional distress, and providing comprehensive follow-up care information and health education to alleviate the anxiety associated with hospital discharge and life after discharge. The challenges of providing nursing care to adolescent and young adult patients differ significantly from those faced in the care of either elderly or pediatric patients. Furthermore, although extensive research has been conducted on mothers diagnosed with cancer, little research has addressed the impact on the paternal role when fathers are diagnosed with cancer, with limited information available regarding their psychological concerns and issues or the impact on family dynamics. The author hopes this case care experience offers an insightful reference and guide for nursing practice that contributes to a better understanding of the psychological aspects of young adult fathers diagnosed with cancer and facilitates more appropriate care in clinical settings.

Human dental mesenchymal stem cells restorate immune response in sera of pemphigus vulgaris patients.

Pemphigus is an IgG-mediated autoimmune condition characterized by autoantibodies targeting desmogleins, leading to acantholysis. Current treatments, including systemic corticosteroids and immunosuppressive drugs, are associated with significant adverse effects. Mesenchymal stem cells (MSCs) offer a promising alternative due to their immunomodulatory properties and low immunogenicity. This study evaluates the immunomodulatory effects of dental follicle mesenchymal stem cells (DF-MSCs) obtained from healthy donors on Pemphigus vulgaris (PV) patients and healthy controls by examining T-cell proliferation, apoptosis, cytokine levels, and anti-desmoglein 1/3 IgG profiles. Peripheral blood mononuclear cells (PBMCs) were isolated from twenty-one symptomatic PV patients and eleven healthy volunteers. DF-MSCs were characterized and differentiated into osteocytes, adipocytes, and chondrocytes. Peripheral blood mononuclear cells (PBMCs) were co-cultured with DF-MSCs, and various assays were conducted to evaluate T-cell proliferation, apoptosis, regulatory T cells, cytokine expression, and autoantibody levels. Results showed that DF-MSC co-cultures significantly reduced lymphocyte proliferation (43.58-16.27%), IL-4 (38.06 ng/L to 32.26 ng/L), TNF-α (32.45 ng/L to 29.41 ng/L), and DSG1 (3.29 ng/ml to 3.00 ng/ml) and DSG3 (262.40 ng/ml to 245.08 ng/ml) levels in PV patients. An increase in regulatory T cells (1.22-3.75%), IL-10 (47.46 pg/ml to 54.94 pg/ml), and IFN-γ (12.39 ng/ml to 19.70 ng/ml) was also observed. No significant changes were noted in healthy controls. These findings suggest that DF-MSCs could potentially offer a curative approach for treating pemphigus by restoring immune balance. However, further clinical trials are necessary to confirm their efficacy.

Value of miR-31 and miR-150-3p as diagnostic and prognostic biomarkers for breast cancer.

BACKGROUND: The most prevalent malignancy among women is breast cancer (BC). MicroRNAs (miRNAs) play a role in the initiation and progression of BC by influencing breast cancer stem cells (BCSCs) but the diagnostic and prognostic roles of those miRNAs on BC patients are still unknown. It was aimed to investigate expression profiles, diagnostic and prognostic potentials of BCSC-related miRNAs in different subtypes (Luminal A and B, HER2 + and TNBC) of BC patients. METHODS AND RESULTS: Expression analysis of 15 BCSC-related miRNAs was performed in 50 breast tumor tissues and 20 adjacent non-tumor tissues obtained from BC patients using the qRT-PCR method. The expression levels of miR-31 and miR-150-3p were significantly upregulated in the tumor tissues compared to the adjacent non-tumor tissues (p < 0.05). miR-31 expression upregulated in the Luminal A and Luminal B group compared to non-tumor tissue (p < 0.05). miR-31 expression was determined to be significantly higher in the Luminal group (Luminal A and B) compared to the aggressive group (HER2 + and TNBC) (p < 0.05). According to the ROC analysis, the area under the curve (AUC) of miR-31 and miR-150-3p were 0.66 with a sensitivity of 68% and a specificity of 70%. A significant inverse correlation was observed between miR-31 expression with metastatic carcinoma status, in situ component, and Ki67 value in tumors, and high miR-150-3p expression was correlated with p63 expression (p < 0.05). CONCLUSION: miR-31 and miR-150-3p have the potential to serve as biomarkers for guiding diagnosis, evaluating prognosis, and metastatic process in patients with BC.

Insights into cytomegalovirus-associated T cell receptors in recipients following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) reactivation is a serious problem in recipients of allogeneic hematopoietic stem cell transplantation. Long-term latency depends on specific T cell immune reconstitution, which identifies various pathogens by T cell receptors (TCRs). However, the mechanisms underlying the selection of CMV-specific TCRs in recipients after transplantation remain unclear. METHODS: Using high-throughput sequencing and bioinformatics analysis, the T cell immune repertoire of seven CMV reactivated recipients (CRRs) were analyzed and compared to those of seven CMV non-activated recipients (CNRs) at an early stage after transplant. RESULTS: The counts of unique complementarity-determining region 3 (CDR3) were significantly higher in CNRs than in CRRs. The CDR3 clones in the CNRs exhibit higher homogeneity compared to the CRRs. With regard to T cell receptor ß-chain variable region (TRBV) and joint region (TRBJ) genotypes, significant differences were observed in the frequencies of TRBV6, BV23, and BV7-8 between the two groups. In addition to TRBV29-1/BJ1-2, TRBV2/BJ2-2, and TRBV12-4/BJ1-5, 11 V-J combinations had significantly different expression levels between CRRs and CNRs. CONCLUSIONS: The differences in TCR diversity, TRBV segments, and TRBV-BJ combinations observed between CNRs and CRRs might be associated with post-transplant CMV reactivation and could serve as a foundation for further research.

Stem cell transplantation in cerebrovascular accidents: A global bibliometric analysis (2000-2023).

BACKGROUND: Cerebrovascular accident (CVA) is a major global contributor to death and disability. As part of its medical management, researchers have recognized the importance of promising neuroprotective strategies, where stem cell transplantation (SCT) is thought to confer advantages via trophic and neuroprotective effects. AIM: To evaluate the current state of research on SCT in patients with CVA, assess key trends and highlight literature gaps. METHODS: PubMed was screened for SCT in CVA-related articles in October 2023, for each country during the period between 2000 and 2023. Using the World Bank data, total population and gross domestic product were collected for comparison. VOSviewer_1.6.19 was used to create the VOS figure using the results of the same query. Graphs and tables were obtained using Microsoft Office Excel. RESULTS: A total of 6923 studies were identified on SCT in CVA, making 0.03% of all published studies worldwide. Approximately, 68% were conducted in high-income countries, with a significant focus on mesenchymal stem cells. The journal "Stroke" featured the largest share of these articles, with mesenchymal SCT having the highest rate of inclusion, followed by hematopoietic SCT. Over time, there has been a noticeable shift from in vitro studies, which assess stem cell proliferation and neurogenesis, to in vivo studies aimed at evaluating efficacy and safety. Additionally, the number of reviews increased along this approach. CONCLUSION: This bibliometric analysis provides a comprehensive guide for physicians and researchers in the field through an objective overview of research activity, and highlights both current trends and gaps. Having a potential therapeutic role in CVA, more research is needed in the future to focus on different aspects of SCT, aiming to reach a better treatment strategy and improve life quality in patients.

Volumetric modulated arc therapy total body irradiation improves toxicity outcomes compared to 2D total body irradiation.

Introduction: Volumetric modulated arc therapy (VMAT) total body irradiation (TBI) allows for greater organ sparing with improved target coverage compared to 2D-TBI. However, there is limited evidence of whether improved organ sparing translates to decreases in toxicities and how its toxicities compare to those of the 2D technique. We aimed to compare differences in toxicities among patients treated with TBI utilizing VMAT and 2D techniques. Methods/materials: A matched-pair single-institution retrospective analysis of 200 patients treated with TBI from 2014 to 2023 was performed. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and compared using log-rank tests. Differences in characteristics and toxicities between the VMAT and 2D cohorts were compared using Fisher's exact test. Results: Of the 200 patients analyzed, 100 underwent VMAT-TBI, and 100 underwent 2D-TBI. The median age for VMAT-TBI and 2D-TBI patients was 13.7 years and 16.2 years, respectively (p = 0.25). In each cohort, 53 patients were treated with myeloablative regimens (8-13.76 Gy), and 47 were treated with non-myeloablative regimens (2-4 Gy). For the entire VMAT-TBI cohort, lung Dmean, kidney Dmean, and lens Dmax were spared to 60.6% ± 5.0%, 71.0% ± 8.5%, and 90.1% ± 3.5% of prescription, respectively. For the non-myeloablative VMAT-TBI cohort, testis/ovary Dmax, brain, and thyroid Dmean were spared to 33.4% ± 7.3%, 75.4% ± 7.0%, and 76.1% ± 10.5%, respectively. For 2D-TBI, lungs were spared using partial-transmission lung blocks for myeloablative regimens. The VMAT-TBI cohort experienced significantly lower rates of any grade of pneumonitis (2% vs. 12%), nephrotoxicity (7% vs. 34%), nausea (68% vs. 81%), skin (16% vs. 35%), and graft versus host disease (GVHD) (42% vs. 62%) compared to 2D-TBI patients. For myeloablative regimen patients, rates of pneumonitis (0% vs. 17%) and nephrotoxicity (9% vs. 36%) were significantly lower with VMAT-TBI versus 2D-TBI (p < 0.01). Median follow-up was 14.3 months, and neither median OS nor PFS for the entire cohort was reached. In the VMAT versus 2D-TBI cohort, the 1-year OS was 86.0% versus 83.0% (p = 0.26), and the 1-year PFS was 86.6% and 80.0% (p = 0.36), respectively. Conclusion: Normal tissue sparing with VMAT-TBI compared to the 2D-TBI translated to significantly lower rates of pneumonitis, renal toxicity, nausea, skin toxicity, and GVHD in patients, while maintaining excellent disease control.

Hematopoietic and leukemic stem cells homeostasis: the role of bone marrow niche.

The bone marrow microenvironment (BMM) has highly specialized anatomical characteristics that provide a sanctuary place for hematopoietic stem cells (HSCs) that allow appropriate proliferation, maintenance, and self-renewal capacity. Several cell types contribute to the constitution and function of the bone marrow niche. Interestingly, uncovering the secrets of BMM and its interaction with HSCs in health paved the road for research aiming at better understanding the concept of leukemic stem cells (LSCs) and their altered niche. In fact, they share many signals that are responsible for interactions between LSCs and the bone marrow niche, due to several biological similarities between LSCs and HSCs. On the other hand, LSCs differ from HSCs in their abnormal activation of important signaling pathways that regulate survival, proliferation, drug resistance, invasion, and spread. Targeting these altered niches can help in better treatment choices for hematological malignancies and bone marrow disorders in general and acute myeloid leukemia (AML) in particular. Moreover, targeting those niches may help in decreasing the emergence of drug resistance and lower the relapse rate. In this article, the authors reviewed the most recent literature on bone marrow niches and their relations with either normal HSCs and AML cells/LSC, by focusing on pathogenetic and therapeutic implications.

Case report: Successful combination of CLL1 CAR-T therapy and hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory acute myeloid leukemia.

The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.

Advanced nano delivery system for stem cell therapy for Alzheimer's disease.

Alzheimer's Disease (AD) represents one of the most significant neurodegenerative challenges of our time, with its increasing prevalence and the lack of curative treatments underscoring an urgent need for innovative therapeutic strategies. Stem cells (SCs) therapy emerges as a promising frontier, offering potential mechanisms for neuroregeneration, neuroprotection, and disease modification in AD. This article provides a comprehensive overview of the current landscape and future directions of stem cell therapy in AD treatment, addressing key aspects such as stem cell migration, differentiation, paracrine effects, and mitochondrial translocation. Despite the promising therapeutic mechanisms of SCs, translating these findings into clinical applications faces substantial hurdles, including production scalability, quality control, ethical concerns, immunogenicity, and regulatory challenges. Furthermore, we delve into emerging trends in stem cell modification and application, highlighting the roles of genetic engineering, biomaterials, and advanced delivery systems. Potential solutions to overcome translational barriers are discussed, emphasizing the importance of interdisciplinary collaboration, regulatory harmonization, and adaptive clinical trial designs. The article concludes with reflections on the future of stem cell therapy in AD, balancing optimism with a pragmatic recognition of the challenges ahead. As we navigate these complexities, the ultimate goal remains to translate stem cell research into safe, effective, and accessible treatments for AD, heralding a new era in the fight against this devastating disease.

ROS responsive conductive microspheres loaded with salvianolic acid B as adipose derived stem cell carriers for acute myocardial infarction treatment.

Stem cell therapy is currently the most promising strategy for the treatment of myocardial infarction. However, the development of injectable cell carriers that can scavenge reactive oxygen species (ROS) in the infarct zone to improve transplanted cell survival remains a challenge. Here, we developed a ROS responsive conductive microsphere based on chitosan (CS) and dextran (DEX) with 4-formylphenylboronic acid (4-FPBA) as a cross-linking agent and the addition of graphite oxide (GO) and the anti-inflammatory agent salvianolic acid B (SalB), as a cell delivery carrier for myocardial infarction. These microspheres were crosslinked by dual dynamic networks of Schiff base and phenylborate bonds. The relationship between CS concentration and microsphere particle size, as well as the biocompatibility, ROS responsiveness, anti-inflammatory properties, and effects on myogenic differentiation of H9C2 cells were fully investigated. The microspheres exhibit good biocompatibility, proliferation promoting, differentiation promoting, antioxidant, and anti-inflammatory properties. When applied to mice myocardial infarction models, the ROS responsive conductive microspheres loaded with SalB and adipose derived stem cells (ADSC) exhibited excellent in vivo repair ability. In addition, they reduced myocardial fibrosis and promoted ventricular wall regeneration by promoting the expression of Connexin 43 (Cx43) and CD31, ultimately reshaping the infarcted myocardium, suggesting their great potential as cell delivery carriers for myocardial infarction treatment.

Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance.

Mitochondrial adaptations dynamically reprogram cellular bioenergetics and metabolism and confer key properties for human cancers. However, the selective regulation of these mitochondrial responses remains largely elusive. Here, inspired by a genetic screening in acute myeloid leukemia (AML), we identify RAS effector RREB1 as a translational regulator and uncover a unique translation control system for nuclear-encoded mitochondrial proteins in human cancers. RREB1 deletion reduces mitochondrial activities and succinate metabolism, thereby damaging leukemia stem cell (LSC) function and AML development. Replenishing complex II subunit SDHD rectifies these deficiencies. Notably, inhibition of complex II re-sensitizes AML cells to venetoclax treatment. Mechanistically, a short RREB1 variant binds to a conserved motif in the 3' UTRs and cooperates with elongation factor eEF1A1 to enhance protein translation of nuclear-encoded mitochondrial mRNAs. Overall, our findings reveal a unique translation control mechanism for mitochondrial adaptations in AML pathogenesis and provide a potential strategy for targeting this vulnerability of LSCs.

[Survey of Preventing Exposure Regarding Sweat in Patients Receiving Antineoplastic Agents at Base Hospitals for Promoting Hematopoietic Stem Cell].

This survey aimed to reveal the actual preventing exposure for handling of clothing and sweat of patients treated with anticancer drugs, following the publication of "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition" (Guideline 2019). A survey was conducted among nurses working at 95 hematopoietic stem cell transplantation promotion base hospitals from September 1, 2023 to October 31, 2023. The response rate was 84.2% (80 facilities). Of the respondents, 45% wore gloves when touching patients' skin to administer anticancer drugs. Almost the nurses identified "urine" and "feces" as fluids on contaminated linen, while 14.1% also identified "sweat." For new staff, the results for preventing exposure education on "if touching the patients' skin" and "if handling clothing and linen" were 23.8% and 34.9%, respectively. This survey shows that nurses may not be following the Guideline 2019 for use of personal protective equipment and handling of clothes. Medical institutions handling anticancer drugs need to educate their staff for preventing occupational exposure.

[Update on treatment strategies for mantle cell lymphoma].

Mantle cell lymphoma (MCL) is a type of lymphoid malignancy that is rare in Japan. MCL is refractory to conventional chemotherapy and has dismal outcomes. Nonetheless, the prognosis of MCL has gradually improved with the advent of autologous stem cell transplantation and BTK inhibitors. First-line therapies incorporating BTK inhibitors are currently under development, and are expected to further improve the prognosis. Nevertheless, subsets with poor prognosis have been identified, including p53 abnormalities (TP53 mutations or deletions), blastoid variant, high MIPI-c, and POD24, and these show resistance to conventional treatments including BTK inhibitors. To overcome these challenges, novel therapies such as CAR-T therapy and combination therapy with BTK and BCL2 inhibitors are being developed, and should soon become clinically available in Japan. The therapeutic landscape for MCL is evolving dynamically, and this article will discuss the future of MCL treatment strategies in Japan.

[Pathogenesis and novel therapies for chronic GVHD].

Treatment for chronic graft-versus-host disease, the most important long-term complication of allogeneic hematopoietic cell transplantation, has changed significantly over the past decade. Development of novel targeted therapies has advanced as objective criteria for the diagnosis and evaluation of chronic GVHD have been established and understanding of the biological pathways to pathogenesis has increased. This paradigm shift is driving chronic GVHD practice significantly toward individualized therapy while minimizing exposure to steroids. Treatment using a variety of novel agents, tailored to each individual patient's condition, is expected to improve quality of life and overall survival by preventing chronic GVHD, controlling disease progression, and maintaining motor and occupational functions. This article reviews the pathogenesis of chronic GVHD and discusses prospects for the treatment of chronic GVHD, along with recently approved drugs and promising drugs in development.

[Thrombopoietin-mediated regulation of hematopoietic stem cells].

Sustaining lifelong hematopoiesis requires maintenance, proliferation, and differentiation of hematopoietic stem cells. Thrombopoietin is a cytokine essential for regulation of hematopoietic stem cells as well as differentiation and maturation of megakaryocytes required for platelet production. Due to these properties, thrombopoietin agonists have been used to treat bone marrow failure syndromes such as aplastic anemia. Through analysis of thrombopoietin gene-deficient mice, my colleagues and I have demonstrated the mechanism of action of thrombopoietin receptor agonists in hematopoietic stem cell maintenance and differentiation. This review focuses on governance of homeostasis in the hematopoietic system by thrombopoietin signaling.

[Allogeneic transplantation as a therapeutic option for atypical chronic myeloid leukemia].

Atypical chronic myeloid leukemia (aCML) is a rare disease classified as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Recent advances in gene mutational profiling have clarified the characteristics of aCML as a disease entity relative to other MDS/MPNs. Although some studies suggest the efficacy of DNA demethylating agents and tyrosine kinase inhibitors, data about these agents are limited due to the small number of patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is only therapeutic option that can provide durable remission for aCML and other MDS/MPNs. Retrospective studies from Europe and Japan revealed the clinical results of allo-HSCT for aCML. This review summarizes the pathogenesis of aCML and the development of allo-HSCT and other therapeutic options.