Editor’s Note: As autumn scents the air with osmanthus blossoms, leading scientists gathered in Kumamoto for an intellectual feast. The 54th Annual Scientific Meeting of the International Society for Experimental Hematology (ISEH 2025) was grandly held from September 24 to 27 in Kumamoto, Japan, drawing world-leading experts in hematology to discuss cutting-edge advances in basic hematology, immunology, stem cell research, and cellular and gene therapies. On the opening day, the much-anticipated “China–Japan Joint Symposium on Stem Cells and Cell Therapy” took place. Co-hosted by the Institute of Hematology, Chinese Academy of Medical Sciences (CAMS) and Kumamoto University, this special session aimed to deepen scientific exchange and cooperation between China and Japan in the fields of stem cell and cellular therapy—ushering in a new era of academic integration and innovation.Launching a New Chapter: Forty Years of Sino–Japanese Exchange in Hematology
The symposium began with opening remarks from Prof. Tao Cheng, Director of the Institute of Hematology, CAMS. He recalled that the last China–Japan Hematology Symposium took place forty years ago, after which academic exchange between the two countries had been relatively limited. Prof. Cheng emphasized that as hematology continues to advance at the frontiers of medicine, establishing a sustained mechanism for Sino–Japanese academic collaboration has become increasingly vital. With support from ISEH, local institutions, and senior scholars including Prof. Toshio Suda and Prof. Jianxiang Wang, this year’s joint symposium focusing on stem cell and cell immunotherapy was successfully convened. He expressed hope that similar meetings could be held annually in alternating host countries, with ISEH and other international organizations participating, thereby strengthening cooperation and generating fruitful outcomes from this historic gathering.
Sparks of Innovation: From Gene Therapy to the Stem Cell Revolution
Prof. Hutan Liu of Wuhan University delivered a compelling presentation titled “Splicing Factor DHX15 Mutations Amplify Leukemia Stem Cell Activity.” Her research focused on the RUNX1::RUNX1T1 subtype of acute myeloid leukemia (AML). The team discovered that DHX15 mutations specifically enhance leukemia stem cell activity in this AML subtype, accelerating disease progression by increasing the stem cell fraction and mitotic activity. Transcriptomic analysis revealed upregulation of genes in the oxidative phosphorylation (OxPhos) pathway, which was validated by Seahorse assays showing increased respiration and ATP production. Based on these findings, the team proposed a targeted OxPhos inhibition strategy—demonstrating that the OxPhos inhibitor Gboxin sensitized mutant cells and, when combined with cytarabine, reversed chemoresistance and stem cell activity. This suggests that DHX15 mutations may serve as biomarkers for therapeutic sensitivity and guide new AML treatment strategies.
Prof. Fumio Arai of Kyushu University presented “Signaling Networks Governing Hematopoietic Stem Cell Quiescence.” He explained that hematopoietic stem cells (HSCs) gradually lose function with aging or prolonged in vitro culture, while the microenvironment maintains quiescence through SCF and angiopoietin-1/Tie2 signaling. RNA sequencing revealed high expression of Foxp2 in quiescent HSCs. Knockout of Foxp2 reduced HSC quiescence and repopulating capacity, whereas overexpression enhanced both. Mechanistically, Foxp2 maintains HSC quiescence by regulating the downstream gene EGR1—with EGR1 overexpression rescuing Foxp2-deficient phenotypes. Angiopoietin-1 was shown to upregulate the Foxp2–EGR1 axis, identifying it as a key pathway governing HSC quiescence and self-renewal. Prof. Arai further noted that modulation of this axis via microenvironmental cues or n-3 polyunsaturated fatty acids (PUFAs) could offer new strategies for improving HSC function.
Dr. Yu Lan from the Institute of Hematology, CAMS, shared her insights on “Early Hematopoietic Development in Primates.” Using single-cell transcriptomic analyses of human (CS11–CS23) and macaque embryos, her team systematically mapped early hematopoietic development, focusing on the emergence and lineage bias of HSC-independent progenitors. They identified yolk sac–derived myeloid-biased (YSMP) and lymphoid-biased (YSLP) progenitors, showing that hematopoietic and immune progenitors emerge earlier in primates than in mice. Notably, lymphoid progenitors exhibited innate lymphoid and monocytic potential even before HSC colonization of the fetal liver. These findings provide a valuable theoretical and data foundation for future research into human hematopoietic development and regeneration.
Prof. Mineo Kurokawa of the University of Tokyo discussed “Development of a Method for Mass Production of Functional Granulocytes Derived from Human iPS Cells.” He explained that granulocyte transfusion therapy (GTX) remains limited by donor burden and insufficient granulocyte yields. His team developed an innovative approach: generating hematopoietic progenitors from iPSCs under VEGF induction, introducing c-Myc, BMI1, and BCL-XL to enhance proliferation, and optimizing cytokine culture conditions. Within ten weeks, the method expanded progenitors to ~50 billion cells, which could differentiate into functional neutrophils within four days—a 5,000-fold improvement over conventional protocols. The AKT2 inhibitor MK-2206 further shortened differentiation to two days. Although immune rejection must still be addressed for universal iPSC sources, this scalable platform provides a powerful solution for GTX and offers potential in anti-cancer and anti-inflammatory applications.
Prof. Feng Xue from the Institute of Hematology, CAMS, presented the latest results of “Adeno-Associated Virus Vector Expressing Factor IX Padua in Treating Hemophilia B in China.” The gene therapy product BBM-H901 employs a liver-specific promoter to express the highly active Factor IX Padua variant. In its Phase I pivotal study, prophylactic prednisone was administered one day prior to infusion. Results showed an average Factor IX activity of ~55%, with 80% of patients achieving complete bleed- and treatment-free status and excellent safety. Compared with international products Hemgenix and Beqvez, BBM-H901 achieved higher FIX activity at lower doses and substantially lower cost. In 2025, it was approved by the NMPA as China’s first gene therapy for hemophilia B, providing patients with a highly effective and safe treatment option.
Prof. Miki Ando of Juntendo University reported on “Development of iPSC-Derived Next-Generation T Cell Therapy for Refractory Tumors.” Her team reconstructed EBV-specific cytotoxic T lymphocytes (CTLs) using T-iPSC technology to generate functional rege-T cells, which exhibited potent cytotoxicity and long-term persistence in vivo. By using CRISPR-Cas9 to delete HLA-I, they developed low-immunogenic, high-efficiency rege-T cells suitable as “off-the-shelf” therapies for EBV-associated lymphomas. The group also engineered dual-antigen CAR rege-T cells, enhancing efficacy against EBV-positive tumors, and GD2 CAR rege-T for small-cell lung cancer, which significantly suppressed tumor growth and prolonged survival in preclinical models. A Phase I clinical trial for EBV-related lymphoma has already begun, marking a potential breakthrough in iPSC-based cell therapy.
Prof. Naoki Hosen from Osaka University gave a talk on “CAR-T and NK Cell Therapy for AML Relapsed After Allogeneic HCT.” He highlighted that post-transplant relapse remains a major challenge, with survival below 20% in non-remission transplants. Screening ~14,000 monoclonal antibodies, his team identified KG2O32, which recognizes AML cells in about half of patients. Using CRISPR screening, they found its target to be HLA-DR, specifically dependent on certain HLA-DRB1 alleles—distinguishing leukemic cells from donor-derived normal cells in mismatched transplants. KG2O32 showed minimal binding to non-hematopoietic tissues, maintaining selectivity even after IFN-γ stimulation. In animal models, KG2O32 CAR-T and CAR-NK cells effectively eradicated AML and achieved 100% survival, demonstrating strong anti-leukemic activity. The team is now advancing clinical trials exploring CAR-based approaches in post-transplant AML.
Prof. Jianxiang Wang of the Institute of Hematology, CAMS, delivered a presentation titled “Integration of CAR-T into Total Therapy of Acute Lymphoblastic Leukemia.” He noted that prognosis for adult ALL remains poor—particularly in patients over 40, whose long-term survival is below 30%. For relapsed/refractory ALL, his group developed CD19 and dual CD19/CD22 CAR-T therapies, achieving remission in ~90% of patients, with 80% reaching MRD negativity and deep molecular response. Building on this success, the team designed the “Ph-negative ALL 2024 protocol” and a combined regimen of olverembatinib, reduced-intensity chemotherapy, and CAR-T for Ph-positive ALL, both showing promising outcomes. A universal CD7 CAR-T is also in development to reduce dependency on allogeneic transplantation. With a comprehensive CAR-T pipeline established, Prof. Wang emphasized that frontline use of CAR-T could markedly extend survival in adult ALL.
Toward the Future: Building a Global Blueprint for Stem Cell and Cellular Therapy
In closing, Prof. Atsushi Iwama of the University of Tokyo delivered the final remarks. He expressed gratitude to all speakers and attendees, noting that audience participation far exceeded expectations and the discussions were highly engaging. Prof. Iwama praised the symposium’s rich and diverse content—from basic science to clinical cell therapy—and thanked Prof. Tao Cheng and his institution for their strong support, as well as Prof. Toshio Suda for his exceptional leadership in coordination and organization. He described the event as a “preparatory meeting” that lays the groundwork for the next day’s main sessions and encouraged participants to continue their academic exchanges while enjoying the cultural charm of Kumamoto—a fitting blend of scientific insight and cross-cultural friendship.
