Machine Perfusion Enables 24-h Preservation of Vascularized Composite Allografts in a Swine Model of Allotransplantation

Marion Goutard; Pierre Tawa; Yanis Berkane; Alec R Andrews; Casie A Pendexter; Reinier J de Vries; Victor Pozzo; Golda Romano; Hyshem H Lancia; Irina Filz von Reiterdank; Nicolas Bertheuil; Ivy A Rosales; Ira Doressa Anne L How; Mark A Randolph; Alexandre G Lellouch; Curtis L Cetrulo Jr; Korkut Uygun

doi:10.3389/ti.2024.12338

Machine Perfusion Enables 24-h Preservation of Vascularized Composite Allografts in a Swine Model of Allotransplantation

Transpl Int. 2024 May 15:37:12338. doi: 10.3389/ti.2024.12338. eCollection 2024.

Authors

Marion Goutard^#^{1

2

3}, Pierre Tawa^#^{1

2

3}, Yanis Berkane^{1

2

3

4

5}, Alec R Andrews^{1

2

3}, Casie A Pendexter^{2

3

6}, Reinier J de Vries^{2

3

6

7}, Victor Pozzo^{1

2

3}, Golda Romano^{1

2

3}, Hyshem H Lancia^{1

2

3}, Irina Filz von Reiterdank^{1

2

3

6

8}, Nicolas Bertheuil^{4

5}, Ivy A Rosales^{9

10}, Ira Doressa Anne L How^{9

10}, Mark A Randolph^{1

2

3}, Alexandre G Lellouch^{1

2

3}, Curtis L Cetrulo Jr^#^{1

2

3}, Korkut Uygun^#^{2

3

6}

Affiliations

¹ Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA, United States.
² Harvard Medical School, Boston, MA, United States.
³ Shriners Children's Boston, Boston, MA, United States.
⁴ Suivi Immunologique des Thérapeutiques Innovantes Laboratory, INSERM U1236, University of Rennes 1, Rennes, France.
⁵ Department of Plastic, Reconstructive, and Aesthetic Surgery, Centre Hospitalier Universitaire de Rennes, Université de Rennes 1, Rennes, France.
⁶ Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.
⁷ Department of Surgery, Amsterdam University Medical Centers-Location AMC, University of Amsterdam, Amsterdam, Netherlands.
⁸ University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
⁹ Immunopathology Research Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.
¹⁰ Department of Pathology, Harvard Medical School, Boston, MA, United States.

^# Contributed equally.

Abstract

The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24 h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.

Keywords: VCA; ischemia-reperfusion injuries; machine perfusion; organ preservation; vascularized composite allotransplantation.

MeSH terms

Allografts
Animals
Composite Tissue Allografts
Graft Survival*
Hindlimb
Models, Animal
Organ Preservation* / methods
Perfusion* / methods
Swine
Transplantation, Homologous
Vascularized Composite Allotransplantation* / methods

Grants and funding

The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of Assistant Secretary of Defense for Health Affairs, through the Reconstructive Transplant Research Program, Technology Development Award under Awards Nos W81XWH-17-1-0437 and W81XWH-17-1-0440 (CC, AL, and KU). This material is partially based upon work supported by the National Science Foundation under Grant No. EEC 1941543. YB was supported by “Fondation des Gueules Cassées” (France) under Award No 06-2021. Partial support from the US National Institutes of Health (R01EB028782) is gratefully acknowledged.