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Acellular Normothermic Machine Perfusion Does not Exacerbate Acute Rejection in Rodent Vascularized Composite
Irina Filz von Reiterdank1,2,3,4, Raphaela Bento1,2,5, Eloi de Clermont-Tonnerre3,4
1Center for Engineering for Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Transplantation Direct
|May 11, 2026
Summary
Normothermic machine perfusion (NMP) delays acute rejection in vascularized composite allotransplantation compared to static cold storage (SCS). This study in a rodent model shows NMP reduces early rejection scores and alters immune cell populations.
Area of Science:
- Transplantation immunology
- Organ preservation techniques
- Surgical innovation
Background:
- Vascularized composite allotransplantation (VCA) faces challenges like limited preservation and high acute rejection rates.
- Ischemia susceptibility of muscle and immunogenicity of skin are key issues in VCA.
- The effect of normothermic machine perfusion (NMP) versus static cold storage (SCS) on acute rejection in VCA is unstudied.
Purpose of the Study:
- To investigate the impact of NMP compared to SCS on acute rejection in a rodent VCA model.
- To assess clinical, histological, and immunological outcomes following different preservation methods.
Main Methods:
- Heterotopic hindlimb transplants were performed in a full-mismatch rodent model.
- Grafts were preserved using either static cold storage (SCS) or normothermic machine perfusion (NMP) for 6 hours.
- Postoperative assessments included clinical scoring, histology, cytokine profiling, and flow cytometry.
Main Results:
- Normothermic machine perfusion (NMP) significantly reduced rejection scores on postoperative day 2 compared to static cold storage (SCS).
- Histology revealed delayed rejection in the NMP group (severe rejection from POD6) versus the SCS group (severe rejection from POD2).
- NMP was associated with early upregulation of interleukin-10 and a reduction in B cell populations.
Conclusions:
- Normothermic machine perfusion (NMP) is associated with a delayed onset of acute rejection compared to static cold storage (SCS) in a rodent VCA model.
- NMP demonstrates potential in mitigating early immune responses in VCA.
- Further research is needed on early rejection mechanisms and long-term graft survival with NMP.
