Vascularized Composite Allotransplantation: Basic Research and Clinical Experience at Chang Gung

Abstract

Vascularized composite allotransplantation (VCA) represents one of the most complex frontiers in reconstructive surgery, requiring simultaneous transfer of multiple tissue types, including skin, muscle, bone, and nerves. Success depends on the multidisciplinary integration of immunology, surgery, rehabilitation, and psychology. Chang Gung Memorial Hospital has established itself as a pioneer in clinical VCA in Taiwan, contributing significantly through innovative basic research and successful clinical outcomes. This review explores our institutional experience, highlighting clinical cases and groundbreaking preclinical research within our comprehensive VCA program.

Keywords

vascularized composite allotransplantation - immunosuppression - tolerance induction - hand transplantation

^* These authors contributed equally to this work.

Publikationsverlauf

Artikel online veröffentlicht:
08. August 2025

• References

• 1 Thuong M, Petruzzo P, Landin L. et al. Vascularized composite allotransplantation - A Council of Europe position paper. Transpl Int 2019; 32 (03) 233-240
• 2 Dubernard JM, Owen E, Herzberg G. et al. Human hand allograft: report on first 6 months. Lancet 1999; 353 (9161): 1315-1320
• 3 Sucher R, Lin CH, Zanoun R. et al. Mouse hind limb transplantation: a new composite tissue allotransplantation model using nonsuture supermicrosurgery. Transplantation 2010; 90 (12) 1374-1380
• 4 Lin CH, Sucher R, Shih YC. et al. The neck as a preferred recipient site for vascularized composite allotransplantation in the mouse. Plast Reconstr Surg 2014; 133 (02) 133e-141e
• 5 Cheng HY, Lin CF, Anggelia MR. et al. Reciprocal donor-recipient strain combinations present different vascularized composite allotransplantation outcomes in rodent models. Plast Reconstr Surg 2023; 151 (06) 1220-1231
• 6 Landin L, Cavadas PC. The mystacial pad flap: a functional facial flap in rats. Ann Plast Surg 2006; 56 (01) 107-108
• 7 Lin CH, Anggelia MR, Cheng HY. et al. The intragraft vascularized bone marrow induces secondary donor-specific mystacial pad allograft tolerance. Front Immunol 2022; 13: 1059271
• 8 Anggelia MR, Lin HC, Cheng CC. et al. Single injection of tacrolimus-loaded thermosensitive hydrogel improves outcomes in vascularized composite allotransplantation. J Drug Deliv Sci Technol 2025; 105: 106626
• 9 Sucher R, Lin CH, Oberhuber R. et al. Hemiface allotransplantation in the mouse. Plast Reconstr Surg 2012; 129 (04) 867-870
• 10 Cardona E, Wang AYL, Loh CYY. et al. A new face subunit transplant model in mice, containing skin, mandible, and oral mucosa for future face vascularized composite allotransplantation studies. Plast Reconstr Surg 2019; 144 (01) 115-123
• 11 Lin CH, Zhang W, Ng TW. et al. Vascularized osteomyocutaneous allografts are permissive to tolerance by induction-based immunomodulatory therapy. Am J Transplant 2013; 13 (08) 2161-2168
• 12 Lin CH, Wang YL, Anggelia MR. et al. Combined Anti-CD154/CTLA4Ig costimulation blockade-based therapy induces donor-specific tolerance to vascularized osteomyocutaneous allografts. Am J Transplant 2016; 16 (07) 2030-2041
• 13 Lin CH, Anggelia MR, Cheng HY. et al. The intragraft vascularized bone marrow component plays a critical role in tolerance induction after reconstructive transplantation. Cell Mol Immunol 2021; 18 (02) 363-373
• 14 Zhang W, Wang Y, Zhong F. et al. Donor derived hematopoietic stem cell niche transplantation facilitates mixed chimerism mediated donor specific tolerance. Front Immunol 2023; 14: 1093302
• 15 Cheng HY, Tay SKL, Wen CJ. et al. Bioimaging of alloantigen-stimulated regulatory T cells in rat vascularized composite allotransplantation. PLoS One 2018; 13 (09) e0203624
• 16 Anggelia MR, Cheng HY, Chuang WY. et al. Unraveling the crucial roles of FoxP3+ regulatory T cells in vascularized composite allograft tolerance induction and maintenance. Transplantation 2021; 105 (06) 1238-1249
• 17 Huang RW, Anggelia MR, Chuang WY, Hsieh YH, Cheng HY, Lin CH. The effect of narrow-band ultraviolet B irradiation on the vascularized composite allotransplantation rat model. Ann Plast Surg 2022; 88 (1s suppl 1): S22-S26
• 18 Lin HC, Anggelia MR, Cheng CC. et al. A mixed thermosensitive hydrogel system for sustained delivery of tacrolimus for immunosuppressive therapy. Pharmaceutics 2019; 11 (08) 11
• 19 Wu IE, Anggelia MR, Lin SY, Chen CY, Chu IM, Lin CH. Thermosensitive polyester hydrogel for application of immunosuppressive drug delivery system in skin allograft. Gels 2021; 7 (04) 7
• 20 Wang AYL, Chen KH, Lin HC. et al. Sustained release of tacrolimus embedded in a mixed thermosensitive hydrogel for improving functional recovery of injured peripheral nerves in extremities. Pharmaceutics 2023; 15 (02) 15
• 21 Anggelia MR, Cheng HY, Lai PC, Hsieh YH, Lin CH, Lin CH. Cell therapy in vascularized composite allotransplantation. Biomed J 2022; 45 (03) 454-464
• 22 Cheng HY, Ghetu N, Huang WC. et al. Syngeneic adipose-derived stem cells with short-term immunosuppression induce vascularized composite allotransplantation tolerance in rats. Cytotherapy 2014; 16 (03) 369-380
• 23 Loh CY, Wang AY, Kao HK, Cardona E, Chuang SH, Wei FC. Episomal induced pluripotent stem cells promote functional recovery of transected murine peripheral nerve. PLoS ONE 2016; 11 (10) e0164696
• 24 Lin JY, Tsai FC, Wallace CG, Huang WC, Wei FC, Liao SK. Combined treatment with regulatory T cells and vascularized bone marrow transplantation creates mixed chimerism and induces donor-specific tolerance to vascularized composite allografts without cytoreductive conditioning. Chimerism 2013; 4 (01) 20-22
• 25 Plock JA, Schnider JT, Zhang W. et al. Adipose- and bone marrow-derived mesenchymal stem cells prolong graft survival in vascularized composite allotransplantation. Transplantation 2015; 99 (09) 1765-1773
• 26 Aviña AE, De Paz D, Huang SC. et al. IL-10 modified mRNA monotherapy prolongs survival after composite facial allografting through the induction of mixed chimerism. Mol Ther Nucleic Acids 2023; 31: 610-627
• 27 Wei HI, Do NT, Din RY, Lin CH, Lin CH. Attitudes of hand surgeons and hand reconstruction patients toward hand allotransplantation in Taiwan. Ann Plast Surg 2020; 84 (1S, suppl 1): S107-S111
• 28 Jablecki J, Kaczmarzyk L, Domanasiewicz A. et al. Result of arm-level upper-limb transplantation in two recipients at 19- and 30-month follow-up. Ann Transplant 2012; 17 (03) 126-132
• 29 Shores JT, Brandacher G, Lee WPA. Hand and upper extremity transplantation: an update of outcomes in the worldwide experience. Plast Reconstr Surg 2015; 135 (02) 351e-360e