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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.
Background:
Vascularized composite allotransplantation faces significant challenges, including limited preservation time and high rates of acute rejection because of the ischemia susceptibility of muscle and immunogenicity of skin. However, no studies have investigated whether normothermic machine perfusion (NMP) has an effect on acute rejection compared with static cold storage (SCS).
Methods:
Heterotopic hindlimb transplants were performed in a full-mismatch model after 6 h of SCS or NMP. Postoperative assessments included clinical scoring, histological examination, cytokine profiling, and flow cytometry of splenocytes and lymphocytes at the end of the study.
Results:
Clinical assessment revealed significantly lower rejection scores in the NMP group on postoperative day (POD) 2 (P = 0.03). Notably, histology indicated delayed rejection, with Banff scores showing severe rejection from POD2 in the SCS group and from POD6 in the NMP group. Cytokine profiling demonstrated early upregulation of anti-inflammatory interleukin-10 in the NMP group at POD1, and flow cytometry showed a reduction in B cell populations.
Conclusions:
While NMP is not a cure-all, it is associated with a delayed onset of acute rejection compared with SCS in a full-mismatch rodent vascularized composite allotransplantation model. Future studies should focus on analysis earlier in the rejection process and on long-term graft survival to further elucidate the mechanism of the effect of NMP on the immune response.
