Nplate (Romiplostim) Restores Blood Counts and Accelerates Wound Healing Following Radiation Combined Injury in Mice

Area of Science:

• Radiation biology
• Regenerative medicine
• Hematology

Background:

• Radiation combined injury (RCI) exacerbates mortality and morbidity compared to isolated radiation injury (RI).
• Nplate (romiplostim), a thrombopoietin receptor agonist, is FDA-approved for hematopoietic acute radiation syndrome (H-ARS).
• The efficacy of Nplate in mitigating RCI is not well understood.

Purpose of the Study:

• To evaluate the effects of Nplate on survival, wound healing, and hematopoietic recovery in a murine model of RCI.
• To determine if Nplate can serve as a medical countermeasure for RCI.

Main Methods:

• Female B6D2F1/J mice were exposed to 9.0 or 9.5 Gy ⁶⁰Co γ-radiation, followed by a full-thickness skin wound.
• A single dose of Nplate (30 µg/kg) or vehicle was administered 24 hours post-irradiation.
• Survival, body weight, wound closure, and hematopoietic parameters (bone marrow histology, CFU assays, CBC, spleen assessment) were analyzed over 30 days.

Main Results:

• Nplate significantly improved 30-day survival after 9.5 Gy RI (75% vs. 30%), but not in RCI groups (65% at 9.0 Gy, 15% at 9.5 Gy).
• Despite no survival benefit in RCI, Nplate significantly accelerated wound closure (54% increase in healing rate) at 9.5 Gy.
• Nplate enhanced bone marrow cellularity, increased megakaryocytes, suppressed IR-induced adipocyte formation, and stimulated hematopoietic and splenic recovery.

Conclusions:

• Nplate effectively mitigates H-ARS and promotes hematopoietic and tissue regeneration.
• Nplate's survival benefit is limited in RCI, likely due to increased systemic stress.
• Managing RCI may necessitate a multi-modal strategy addressing GI-ARS, inflammation, and endothelial dysfunction.