Inefficient delivery is a major obstacle to the development of peptide-based drugs targeting the intracellular compartment. We recently showed that selectively inhibiting integrin outside-in signaling using a peptide (mP6) derived from the Gα₁₃-binding ExE motif within the integrin β₃ cytoplasmic domain had antithrombotic effects. Here, we engineered lipid-stabilized, high-loading peptide nanoparticles (HLPN), in which a redesigned ExE peptide (M3mP6) constituted up to 70% of the total nanoparticle molarity, allowing efficient in vivo delivery. We observed that M3mP6 HLPN inhibited occlusive thrombosis more potently than a clopidogrel/aspirin combination without adverse effects on hemostasis in rodents. Furthermore, M3mP6 HLPN synergized with P2Y12 receptor inhibitors or the clopidogrel/aspirin combination in preventing thrombosis, without exacerbating hemorrhage. M3mP6 HLPN also inhibited intravascular coagulation more potently than the P2Y12 inhibitor cangrelor. Postischemia injection of M3mP6 HLPN protected the heart from myocardial ischemia–reperfusion injury in a mouse model. This study demonstrates an efficient in vivo peptide delivery strategy for a therapeutic that not only efficaciously prevented thrombosis with minimal bleeding risk but also protected from myocardial ischemia–reperfusion injury in mice.

Hematopoietic stem cell transplantation is an effective regenerative therapy for many malignant, inherited, or autoimmune diseases. However, our understanding of reconstituted hematopoiesis in transplant patients remains limited. Here, we uncover the reconstitution dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at single-cell resolution after transplantation. Transplanted HSPCs underwent rapid and measurable changes during the first 30 days after transplantation, characterized by a strong proliferative response on the first day. Transcriptomic analysis of HSPCs enabled us to observe that immunoregulatory neutrophil progenitors expressing high levels of the S100A gene family were enriched in granulocyte colony-stimulating factor–mobilized peripheral blood stem cells. Transplant recipients who developed acute graft-versus-host disease (aGVHD) infused fewer S100A ^high immunoregulatory neutrophil progenitors, immunophenotyped as Lin ^- CD34 ⁺ CD66b ⁺ CD177 ⁺ , than those who did not develop aGVHD. Therefore, our study provides insights into the regenerative process of transplanted HSPCs in human patients and identifies a potential criterion for identifying patients at high risk for developing aGVHD early after transplant.

Survival of neutrophils is prolonged, and their function is preserved by simultaneously targeting multiple cell death pathways.

Autologous hematopoietic stem cell transplantation (ASCT) remains an important postremission treatment for acute leukemia (AL). It is known that some prognostic factors, such as age, cytogenetic and molecular risk stratification, and minimal residual disease (MRD) status, are closely related to clinical outcomes following ASCT. Moreover, there are multiple measurements, including pretransplant treatment, stem cell mobilization and collection, conditioning regimens, and maintenance treatment after transplantation, that can affect prognosis after ASCT. Our clinical practice of ASCT should be better standardized to further improve patient outcomes. This review outlines optimization and quality control measures for ASCT developed at the Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences, the first established and largest autologous stem cell transplant center in China. These measures will enhance the development of best practices and strategies for AL ASCT therapies, thereby improving patient outcomes.

The delayed platelet engraftment associated with allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a common complication and often results in increased transplant‐related complications. A single‐center, prospective, investigator‐initiated pilot study was conducted to explore whether herombopag, a second generation thrombopoietin‐receptor agonist, would promote platelet engraftment after allo‐HSCT. Between 2/2022 and 06/2022, 17 individuals (median age 39; range 15–58 years) with hematological malignancies were enrolled. Herombopag was given for a median of 22 (range 14–61) days at a dose of 7.5 mg/d. The median time to neutrophil >500/μl was 11 (range 9–19) days. The median time to platelet >20 000/μl and >50 000/μl was 13 (range 8–22), and 20 (range 14–45) days, respectively. Compared with historical controls, the cumulative incidence of platelet engraftment after HSCT was significantly higher in the herombopag group (>20 000/μl at day +21, 88% vs 65%, p = .003; >50 000/μl at day +30, 65% vs. 43%, p = .001). Herombopag also reduced the units of platelet transfusion within 30 days post‐SCT (3.6 ± 2.5 vs. 5.4 ± 3.2 U, p = .01). In conclusion, it seems likely that herombopag could enhance platelet engraftment after allo‐HSCT.