Subscribe to RSS
Download PDF
DOI: 10.1055/s-0044-1788812
Development of a Porcine VCA Model Using an External Iliac Vessel-Based Vertical Rectus Abdominus Myocutaneous Flap
Funding U.S. Department of Health and Human Services, National Institutes of Health, Office of Strategic Coordination, Common Fund NIH/NCATS Colorado CTSA Grant Number T32 TR004367 and UM1 TR004399.Department of Defense CDMRP × FY21 Reconstructive Transplant Research Program: W81XWH2210927 (C.A.H.). The content is the authors' sole responsibility and does not necessarily represent official DOD or NIH views.
Abstract
Background Vascularized composite allotransplantation (VCA) involves transplanting a functional and anatomically complete tissue graft, such as a hand or face, from a deceased donor to a recipient. Although clinical VCA has resulted in successful outcomes, high rates of acute rejection and increased requirements for immunosuppression have led to significant long-term complications. Of note, immunosuppressed graft recipients are predisposed to infections, organ dysfunction, and malignancies. The long-term success of VCA grafts requires the discovery and implementation of unique approaches that avoid these complications altogether. Here, we describe our surgical technique and initial experience with a reproducible heterotopic porcine VCA model for the preclinical assessment of approaches to improve graft outcomes.
Methods Six heterotopic porcine allogeneic vertical rectus abdominis myocutaneous flap transplants were performed using Sinclair donors and Yucatan recipients. Immunosuppressive therapy was not used. Each flap was based on the left external iliac vessel system. Animals were followed postoperatively for surgery-related complications.
Results The six pigs underwent successful VCA and were euthanized at the end of the study. Each flap demonstrated complete survival following vessel anastomosis. For the allogeneic recipients, on average, minimal erythema and healthy flap color were observed from postoperative days 1 to 4. There were no surgery-related animal deaths or complications.
Conclusion We have developed a reproducible, technically feasible heterotopic porcine VCA model based on the left external iliac vessel system. Our results demonstrate this model's potential to improve VCA graft outcomes by exploring tolerance induction and rejection biomarker discovery in preclinical studies.
Keywords
vascularized composite allotransplantation - large animal model - swine - vertical rectus abdominis myocutaneous flap - external iliac vessels* These authors contributed equally.
** These authors contributed equally as co-senior authors.
Publication History
Received: 27 February 2024
Accepted: 10 July 2024
Article published online:
06 August 2024
© 2024. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Weissenbacher A, Hautz T, Pratschke J, Schneeberger S. Vascularized composite allografts and solid organ transplants: similarities and differences. Curr Opin Organ Transplant 2013; 18 (06) 640-644
- 2 Iske J, Nian Y, Maenosono R, Maurer M, Sauer IM, Tullius SG. Composite tissue allotransplantation: opportunities and challenges. Cell Mol Immunol 2019; 16 (04) 343-349
- 3 Lloyd MS, Teo TC, Pickford MA, Arnstein PM. Preoperative management of the amputated limb. Emerg Med J 2005; 22 (07) 478-480
- 4 Swearingen B, Ravindra K, Xu H, Wu S, Breidenbach WC, Ildstad ST. Science of composite tissue allotransplantation. Transplantation 2008; 86 (05) 627-635
- 5 Huelsboemer L, Kauke-Navarro M, Reuter S. et al. Tolerance induction in vascularized composite allotransplantation-a brief review of preclinical models. Transpl Int 2023; 36: 10955
- 6 Kauke M, Safi AF, Panayi AC. et al. A systematic review of immunomodulatory strategies used in skin-containing preclinical vascularized composite allotransplant models. J Plast Reconstr Aesthet Surg 2022; 75 (02) 586-604
- 7 Siemionow M, Nasir S. Chimerism and bone marrow based therapies in transplantation. Microsurgery 2007; 27 (05) 510-521
- 8 Shengwu Z, Qingfeng L, Hao J. et al. Developing a canine model of composite facial/scalp allograft transplantation. Ann Plast Surg 2007; 59 (02) 185-194
- 9 Kirk AD. Crossing the bridge: large animal models in translational transplantation research. Immunol Rev 2003; 196: 176-196
- 10 Steinmuller D. Skin allograft rejection by stable hematopoietic chimeras that accept organ allografts sill is an enigma. Transplantation 2001; 72 (01) 8-9
- 11 Mathes DW, Randolph MA, Solari MG. et al. Split tolerance to a composite tissue allograft in a swine model. Transplantation 2003; 75 (01) 25-31
- 12 El-Mrakby HH, Milner RH. The vascular anatomy of the lower anterior abdominal wall: a microdissection study on the deep inferior epigastric vessels and the perforator branches. Plast Reconstr Surg 2002; 109 (02) 539-543 , discussion 544–547
- 13 Leto Barone AA, Leonard DA, Torabi R. et al. The gracilis myocutaneous free flap in swine: an advantageous preclinical model for vascularized composite allograft transplantation research. Microsurgery 2013; 33 (01) 51-55
- 14 Ozer K, Rojas-Pena A, Mendias CL, Bryner B, Toomasian C, Bartlett RH. Ex situ limb perfusion system to extend vascularized composite tissue allograft survival in swine. Transplantation 2015; 99 (10) 2095-2101
- 15 Villamaria CY, Rasmussen TE, Spencer JR, Patel S, Davis MR. Microvascular porcine model for the optimization of vascularized composite tissue transplantation. J Surg Res 2012; 178 (01) 452-459
- 16 Etra JW, Fidder SAJ, Frost CM. et al. Latissimus dorsi myocutaneous flap procedure in a swine model. J Invest Surg 2021; 34 (12) 1289-1296
- 17 Elgendy TY, Waldner M, Zhang W. et al. Tacrolimus before CTLA4Ig and rapamycin promotes vascularized composite allograft survival in MGH miniature swine. Transpl Immunol 2022; 75: 101696
- 18 Chung JH, Cheon JH, Kim MS. et al. Effects of vasopressors on circulation in the porcine abdominal island flap model. J Plast Reconstr Aesthet Surg 2019; 72 (10) 1653-1660
- 19 Waldner M, Elgendy TY, Kim DY. et al. Heterotopic transplantation of allogeneic vertical rectus abdominis myocutaneous flaps in miniature swine. J Surg Res 2020; 254: 175-182
- 20 Mathes DW, Noland M, Graves S, Schlenker R, Miwongtum T, Storb R. A preclinical canine model for composite tissue transplantation. J Reconstr Microsurg 2010; 26 (03) 201-207
- 21 Feng L, Dumoulin CL, Dashnaw S. et al. Transfemoral catheterization of carotid arteries with real-time MR imaging guidance in pigs. Radiology 2005; 234 (02) 551-557
- 22 Schweizer R, Oksuz S, Banan B, Gorantla V, Fontes P. Subnormothermic machine perfusion (Snmp) with a novel hemoglobin-based oxygen carrier (Hboc) solution for ex vivo preservation in vascularized composite allotransplantation (Vca). Abstract: 8.30. Plast Reconstr Surg Glob Open 2017; 5 (1 Suppl): 25-26
- 23 De Simone B, Sartelli M, Coccolini F. et al. Intraoperative surgical site infection control and prevention: a position paper and future addendum to WSES intra-abdominal infections guidelines. World J Emerg Surg 2020; 15 (01) 10
- 24 Leonard DA, Kurtz JM, Mallard C. et al. Vascularized composite allograft tolerance across MHC barriers in a large animal model. Am J Transplant 2014; 14 (02) 343-355
- 25 Kuo YR, Sacks JM, Lee WP. et al. Porcine heterotopic composite tissue allograft transplantation using a large animal model for preclinical studies. Chang Gung Med J 2006; 29 (03) 268-274
- 26 Kotsougiani D, Willems JI, Shin AY, Friedrich PF, Hundepool CA, Bishop AT. A new porcine vascularized tibial bone allotransplantation model. Anatomy and surgical technique. Microsurgery 2018; 38 (02) 195-202
- 27 Milusev A. The Influence of Donor Lymph Nodes on Immune Rejection and Tolerance in Vascularized Composite Allotransplantation. 2019 . Accessed July 19, 2024 at: https://wwwcvrcunibech/e286839/e780593/20190114_MasterThesisAnastasiaMilusev.pdf
- 28 Kuo YR, Shih HS, Lin CC. et al. Swine hemi-facial composite tissue allotransplantation: a model to study immune rejection. J Surg Res 2009; 153 (02) 268-273
- 29 Suchyta MA, Morsy M, Mardini S, Moran SL. Advances in peripheral nerve regeneration as it relates to VCA, Vascularized Composite Allotransplantation. Vascularized Composite Allotransplantation 2016; 3 (01) 75-88
- 30 Wu C, Rwei AY, Lee JY. et al. A wireless near-infrared spectroscopy device for flap monitoring: proof of concept in a porcine musculocutaneous flap model. J Reconstr Microsurg 2022; 38 (02) 96-105
- 31 Bai W, Guo H, Ouyang W. et al. Intramuscular near-infrared spectroscopy for muscle flap monitoring in a porcine model. J Reconstr Microsurg 2022; 38 (04) 321-327
- 32 Lu D, Moritz W, Arafa HM. et al. Intramuscular microvascular flow sensing for flap monitoring in a porcine model of arterial and venous occlusion. J Reconstr Microsurg 2023; 39 (03) 231-237
- 33 Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 2002; 10 (06) 620-630
- 34 Sullivan SK, Dellacroce F, Allen R. Management of significant venous discrepancy with microvascular venous coupler. J Reconstr Microsurg 2003; 19 (06) 377-380