2-AG-loaded and bone marrow-targeted PCL nanoparticles as nanoplatforms for hematopoietic cell line mobilization.

BACKGROUND: The use of mobilizing agents for hematopoietic stem cell (HSC) transplantation is insufficient for an increasing number of patients. We previously reported lipid made endocannabinoid (eCB) ligands act on the human bone marrow (hBM) HSC migration in vitro, lacking long term stability to be therapeutic candidate. In this study, we hypothesized if a novel 2-AG-loaded polycaprolactone (PCL)-based nanoparticle delivery system that actively targets BM via phosphatidylserine (Ps) can be generated and validated. METHODS: PCL nanoparticles were prepared by using the emulsion evaporation method and characterized by Zetasizer and scanning electron microscopy (SEM). The encapsulation efficiency and release profile of 2-AG were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The presence of cannabinoid receptors (CBRs) in HSCs and monocytes was detected by flow cytometry. Cell morphology and viability were assessed using transmission electron microscopy (TEM), SEM, and the WST-1 viability assay. The migration efficacy of the 2-AG and 2-AG-loaded nanoparticle delivery system on HSCs and HPSCs (TF-1a and TF-1) and monocytes (THP-1) was evaluated using a transwell migration assay. RESULTS: The 140-225 nm PCL nanoparticles exhibited an increasing polydispersity index (PDI) after the addition of Ps and 2-AG, with a surface charge ranging from - 25 to -50 mV. The nanoparticles released up to 36% of 2-AG within the first 8 h. The 2-AG-Ps-PCL did not affect cellular viability compared to control on days 5 and 10. The HSCs and monocytes expressed CB1R and CB2R and revealed increased migration to media containing 1 µM 2-AG-Ps-PCL compared to control. The migration rate of the HSCs toward monocytes incubated with 1 µM 2-AG-Ps-PCL was higher than that of the monocytes of control. The 2-AG-Ps-PCL formulation provided a real time mobilization efficacy at 1 µM dose and 8 h time window via a specific CBR agonism. CONCLUSION: The newly generated and validated 2-AG-loaded PCL nanoparticle delivery system can serve as a stable, long lasting, targeted mobilization agent for HSCs and as a candidate therapeutic to be included in HSC transplantation (HSCT) protocols following scale-up in vivo preclinical and subsequent clinical trials.

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.

In vivo dosimetry of total body irradiation patients: A 10 year retrospective analysis.

Myeloablative Total Body Irradiation (TBI) used in our Institution, as part of the conditioning scheme for haematopoietic stem cell transplantation, is an extended-distance supine technique that has been implemented using a 15 MV LINAC beam, lead lung compensators, PMMA, and water bolus to improve homogeneity. This study reviews in-vivo dosimetry (IVD) over 10 years of treatments, assessing the technique's robustness, accuracy, and efficiency. A 2-lateral opposite fields plan was calculated from planning CT with validated Oncentra TPS (Elekta AB, Sweden). Monitor units (MUs), lung compensators shape and thickness were calculated to deliver the prescription dose (12 Gy in 6 bi-daily fractions or 9.9 Gy in 3 daily fractions) to the patient's abdomen midline at the umbilical level, maintaining lung dose within ±5 % range of prescription. Data from 103 patients, of which more than 87 % were pediatric, were retrieved and analyzed for a total of 537 treatment fractions. The impact of IVD omission was evaluated, supposing doing it only once or in the first two fractions, if necessary. Median ΔMU from planned was -1.2 %. Median percentage dose deviation from prescription in 6 anatomical regions was below 2 %. IVD omission could have resulted in an increase of 7 patients registering at least one anatomical region outside the ±5 % dose range at the end of treatment. It is possible to confirm the implemented technique's robustness and accuracy in delivering the prescribed dose under IVD monitoring. Nevertheless, this technique and associated IVD are time-consuming and IVD omission could be assessed with limited drawbacks.

[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.

[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.

CRISPR/Cas9 in the treatment of sickle cell disease (SCD) and its comparison with traditional treatment approaches: a review.

Sickle cell disease (SCD) is a common hereditary blood disorder that profoundly impacts individuals' health, causing chronic pain, anemia, organ damage, increased susceptibility to infections, and social and psychological effects. Over the years, advances in treatment have improved the long-term outcomes of SCD patients. However, problems such as limited access to hematopoietic stem cell transplantation (HSCT) and potential complications associated with the available therapies underscore the importance of continued research and development. The recent FDA approval of Casgevy (Exagamglogene autotemcel), a genetic therapy based on CRISPR/Cas9 technology, demonstrates a comprehensive effort to address the complexity of SCD using new technologies. This review explores the potential of CRISPR/Cas9 for treating SCD and evaluates its efficacy, safety, and long-term outcomes compared to traditional treatment approaches. Long-term research is needed to comprehensively assess the safety, effectiveness, and inclusion of CRISPR/Cas9, ensuring its overall efficacy.

Long-Term Survival and Immune Reconstitution of Donor-Derived Chimeric Antigen Receptor T-Cell Therapy for Childhood Molecular Relapse of B-Cell Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (n = 3) showed a trend of higher 3-year leukemia-free survival and 3-year overall survival than those who did not (n = 8; 100% vs. 75.0%; 95% CI, 45.0-104.9%; p = 0.370). No treatment-related mortalities were observed. Among patients who did not bridge to second-HSCT and remained in complete remission until the last follow-up (n = 6), five of them had not recovered normal immunoglobulin concentrations with a median follow-up of 43 months. CAR-T therapy may be a safe and effective treatment strategy to improve survival after allo-HSCT; however, the problem of prolonged hypogammaglobulinemia in patients who do not bridge to second-HSCT is worth noting.

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.

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.

Epigenetic regulation of hematopoietic stem cell fate.

Hematopoietic stem cells (HSCs) sustain blood cell production throughout the mammalian life span. However, it has become clear that at the single cell level a subset of HSCs is stably biased in their lineage output, and that such heterogeneity may play a key role in physiological processes including aging and adaptive immunity. Analysis of chromatin accessibility, DNA methylation, and histone modifications has revealed that HSCs with different lineage bias exhibit distinct epigenetic traits inscribed at poised, lineage-specific enhancers. This allows for lineage priming without initiating lineage-specific gene expression in HSCs, controlling lineage bias while preserving self-renewal and multipotency. Here, we review our current understanding of epigenetic regulation in the establishment and maintenance of HSC fate decisions under different physiological conditions.

The Effect of High Intensity Interval Exercise on Platelet Engraftment in Autologous Bone Marrow Transplantation (BMT).

Background: Thrombocytopenia is a frequent complication after hematopoietic stem cell transplantation (HSCT). Although platelet transfusion is the most used treatment for severe thrombocytopenia, it is associated with well-established risks. High-intensity interval exercise (HIIE) results in thrombocytosis. Therefore, this study aimed to reduce thrombocytopenia by increasing platelet count through exercise. Materials and Methods: Twenty lymphoma and multiple myeloma patients were divided into HIIE and control groups. To determine the maximal exercise capacity, patients in the HIIE group performed a graded exercise test. All patients received granulocyte colony-stimulating factor for 5 days, followed by a HIIE trial. After 5 min warm up at 10 to 20% of peak power, patients in the HIIE group performed an HIIE protocol that included 12 intervals of one-minute work at 100% peak power interspersed by one-minute active rest at 20% of peak power. Patients in the control group were seated for the same duration without any physical activity. Two blood samples were taken before and immediately after the trials and were analyzed for measuring complete blood count. Results: Platelet count on the day of platelet engraftment in the HIIE group was significantly higher than in the control group (P=0.02). Single-donor platelet transfusion was significantly lower in the HIIE group than in the control group (P=0.05). Conclusion: Based on the findings of the present study, a short bout of HIIE had a positive effect on platelet engraftment through thrombocytosis and reduced platelet transfusion and its complications, which could be a useful strategy for HSCT patients.

The Relationship between the Lifestyle of the Allogeneic Stem Cell Donors and the Number of Donated CD34+ and CD3+ Cells.

Background: Hematopoietic stem cell transplantation (HSCT) is considered as the last treatment option in many life-threatening diseases. The number of donated cells can affect transplantation success. This study attempted to investigate the relationship between the health-promoting lifestyle of allogeneic stem cell donors and the number of donated CD34+ and CD3+ cells. Materials and Methods: The study was a descriptive correlational study in which 100 peripheral blood stem cells donors participated. A demographic form and health-promoting lifestyle profile-II questionnaire were distributed to participants, and then cell separation was started. Afterward, the results of CD34 + and CD3 + cell counts, as well as other clinical parameters of the participants, were recorded. The collected data were analyzed by descriptive and analytical statistical methods. Results: The results showed that the mean total health-promoting lifestyle profile score for hematopoietic stem cell donors was 2.876±0.461. There was no significant relationship between the health- promoting lifestyle score and the number of CD34+, CD3+ cells and CD3+/CD34+ ratio. A positive and significant correlation was found between the weight of the donors and the number of CD34+ (P < 0.001) and CD3+ cells (P = 0.001). The number of CD34+ cells was significantly different between women and men (P = 0.009). Conclusion: Lifestyle had no significant effect on the number of CD3+/CD34+ cells. Moreover, the number of CD34+ cells was significantly higher in men, so males should be preferentially recruited as donors for the HSCT procedure.

Recovery of physical function, muscle mass, and quality of life in patients undergoing allogeneic hematopoietic stem cell transplantation.

This study aimed to investigate the recovery of physical function, muscle mass, and quality of life (QOL) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients 1 year after the procedure. A total of 71 patients who underwent allo-HSCT at our institution between February 2010 and June 2020, for whom a physical therapy assessment could be performed before allo-HSCT, at discharge, and 1 year after the procedure, were included. Exercise therapy during hospitalization was provided individually by a physical therapist, and exercise was self-administered after discharge. One year after allo-HSCT, handgrip strength and results of the 6-minute walk test recovered to pre-HSCT levels. However, muscle mass 1 year after allo-HSCT did not reach the pre-HSCT level. All subscales of QOL, 1 year after allo-HSCT, recovered to pre-HSCT levels, but only two of the eight subscales recovered to the national standard of 50. Multivariate analysis revealed factors associated with the recovery of physical function, muscle mass, and QOL, hemoglobin levels and albumin levels, especially among men. In contrast, factors that negatively affected recovery were age, acute graft-versus-host disease, and pre-HSCT intensity conditioning. The results suggest a potential recovery in handgrip strength, endurance, and QOL 1 year after allo-HSCT.

Decitabine-based treatment strategy improved the outcome of HSCT in JMML: a retrospective cohort study.

Introduction: Pre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients. Methods: This retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival. Results: There were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002). Conclusion: Implementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments.

Excessive cleavage of von Willebrand factor multimers by ADAMTS13 may predict the progression of transplant-associated thrombotic microangiopathy.

Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of hematopoietic stem cell transplantation and is characterized by severe thrombocytopenia, hemolytic anemia, and organ dysfunction. In response to several possible triggers, dynamic multimetric change in von Willebrand factor (VWF) may contribute to inducing microthrombi in circulation in TA-TMA. Objectives: By performing VWF multimer analysis and measuring VWF-degradation product (DP), we unraveled the relationship between multimeric changes in circulating VWF and the pathogenesis of TA-TMA. Methods: This study analyzed 135 plasma samples from 14 patients who underwent allogeneic hematopoietic stem cell transplantation at a single institute. VWF-associated markers, namely VWF:antigen (VWF:Ag), VWF-DP/VWF:Ag ratio, VWF:ristocetin cofactor activity, VWF:ristocetin cofactor activity/VWF:Ag ratio, and ADAMTS13 activity, were analyzed in these samples collected every 7 days. Results: There were 2 patients with definite thrombotic microangiopathy (TMA) and 6 patients who presented with probable TMA that did not progress to definite TMA. Each plasma sample was classified into 3 groups: definite TMA, probable TMA, and non-TMA. VWF multimer analysis showed the absence of high-molecular-weight VWF multimers in probable TMA, whereas the appearance of unusually large VWF multimers was observed in definite TMA. The median value of the VWF-DP/VWF:Ag ratio in probable TMA was elevated to 4.17, suggesting that excessive cleavage of VWF multimers by VWF cleaving enzyme, ADAMTS13, resulted in the loss of high-molecular-weight VWF multimers. Conclusion: During the transition from probable to definite TMA, drastic VWF multimer changes imply a switch from bleeding to thrombotic tendencies. Extensive VWF-DP and VWF multimer analyses provided novel insights.

Navigating uncharted waters: assessing the impact of the COVID-19 pandemic on hematopoietic stem cell transplantation: challenges and innovations.

The COVID-19 pandemic has significantly impacted hematopoietic stem cell transplantation (HSCT), necessitating adaptations across pre-transplant, transplantation, and post-transplant phases. HSCT recipients with compromised immune systems face heightened risks of severe COVID-19 outcomes, including increased mortality. The pandemic prompted significant changes in treatment strategies, with many patients experiencing delays or deferrals in autologous stem cell transplantation (ASCT), alongside adjustments to chemotherapy regimens to prevent disease recurrence. Clinical practices have evolved to address pandemic-related challenges, including a decrease in allo-HSCT procedures, a shift towards using domestic donors and peripheral blood stem cells over bone marrow grafts, and integration of telemedicine to reduce patient burden. These adaptations aim to balance COVID-19 exposure risks with the need for lifesaving HSCT. Innovations in response to the pandemic include stringent infection control measures, modified conditioning regimens, and revised post-transplant care protocols to mitigate infection risks. The importance of optimizing antiviral treatments, exploring new immunomodulatory interventions, and researching broadly neutralizing antibodies for HSCT recipients has been underscored. Despite the difficulties, the pandemic has catalyzed significant learning and innovation in HSCT practices, emphasizing the need for ongoing adaptation and research to protect this vulnerable patient population.

Cardiovascular Disease After Hematopoietic Stem Cell Transplantation in Adults: JACC: CardioOncology State-of-the-Art Review.

The use of hematopoietic cell transplantation (HCT) has expanded in the last 4 decades to include an older and more comorbid population. These patients face an increased risk of cardiovascular disease after HCT. The risk varies depending on several factors, including the type of transplant (autologous or allogeneic). Many therapies used in HCT have the potential to be cardiotoxic. Cardiovascular complications after HCT include atrial arrhythmias, heart failure, myocardial infarction, and pericardial effusions. Before HCT, patients should undergo a comprehensive cardiovascular assessment, with ongoing surveillance tailored to their individual level of cardiovascular risk. In this review, we provide an overview of cardiotoxicity after HCT and outline our approach to risk assessment and ongoing care.

Acute effects of TLR3 agonist Poly(I:C) on bone marrow hematopoietic progenitor cells in mice.

Hematopoietic progenitor cells (HPCs) in bone marrow with limited abilities for self-renewal and differentiation continuously supply hematopoietic cells through life. When suffering infection or inflammation, HPCs will actively proliferate to provide differentiated hematopoietic cells to maintain hematopoietic homeostasis. Poly(I:C), an agonist of TLR3, can specifically activate Type I interferon (IFN-I) signaling which exerts anti-inflammatory effects and influence hematopoiesis after infection. However, the effects of Poly(I:C)-induced IFN-I on the bone marrow hematopoietic system still deserve attention. In this study, our results revealed the efficacy of the IFN-I model, with a remarkably decrease in HPCs and a sharp elevation in LSKs numbers after single dose of Poly(I:C) injection. Apoptotic ratios of HPCs and LSKs significantly increased 48 h after Poly(I:C) treatment. Application of Poly(I:C) prompted the transition of HPCs and LSKs from G0 to G1 phases, potentially leading to the accelerated exhaustion of HPCs. From the cobblestone area-forming cell (CAFC) assay, we speculate that Poly(I:C) impairs the differentiation capacity of HPCs as well as their colony-forming ability. RT-qPCR and immunohistochemistry revealed significant upregulation of IFN-I associated genes and proteins following Poly(I:C) treatment. In conclusion, a single dose of Poly(I:C) induced an acute detrimental effect on HPCs within 48 h potentially due to TLR3 engagement. This activation cascaded into a robust IFN-I response emanating from the bone marrow, underscoring the intricate immunological dynamics at play following Poly(I:C) intervention.