TGF-b1-Triggered Maladaptive Bone Marrow Endothelium Impedes Hematopoietic Recovery

Research at Peking University People's Hospital has uncovered a critical role of TGF-b1 in driving maladaptive bone marrow endothelium, characterized by defective vascular regeneration and impaired hematopoietic-supporting abilities. The study's findings suggest that TGF-b1 activation drives maladaptive bone marrow endothelial cells, leading to a suppression of hematopoietic-supportive factors and the upregulation of epithelial-mesenchymal transition mediators. Clinically, bone marrow endothelial cells from patients with poor graft function post-transplantation exhibited hyperactivated TGF-b1 signaling. In vitro experiments revealed that TGF-b1 inhibition restored the function of maladaptive bone marrow endothelial cells from these patients.

Key Takeaways:

• TGF-b1 activation drives maladaptive bone marrow endothelial cells, characterized by defective vascular regeneration and impaired hematopoietic-supporting abilities.
• Maladaptive bone marrow endothelial cells from patients with poor graft function post-transplantation exhibited hyperactivated TGF-b1 signaling.
• TGF-b1 inhibition restored the function of maladaptive bone marrow endothelial cells from patients with poor graft function post-transplantation.
• The study's findings suggest that TGF-b1 may be a critical driver of bone marrow endothelium maladaptation.
• A prospective single-arm study involving luspatercept, a TGF-b ligand trap, demonstrated the significant promotion of multilineage hematopoiesis recovery in post-transplantation patients (NCT05629260).
• The study's conclusions highlight the therapeutic potential of TGF-b1 pathway inhibition for hematopoietic regeneration via bone marrow endothelium remodeling.

Statistics:

• 1-16: The journal article Signal Transduction and Targeted Therapy published the study's findings in their October edition.
• 10: The year in which the study's findings were published.
• 1: The volume number of the journal Signal Transduction and Targeted Therapy.
• 155: The page number where the news report was published in Hematology Week.

Sources:

• TGF-b1-triggered maladaptive bone marrow endothelium impedes hematopoietic recovery. Signal Transduction and Targeted Therapy, 2025,10(1):1-16.
• Peking University People's Hospital Researchers Report Research in Gene Therapy (TGF-b1-triggered maladaptive bone marrow endothelium impedes hematopoietic recovery). Hematology Week. October 27, 2025; p 155.
• NCT05629260: A prospective single-arm study involving luspatercept, a TGF-b ligand trap, demonstrated the significant promotion of multilineage hematopoiesis recovery in post-transplantation patients.