Page 92 - Read Online

Wang et al. Plast Aesthet Res 2018;5:10 I http://dx.doi.org/10.20517/2347-9264.2017.90 Page 3 of 10

of the grafts resulting in rupture as well. With the limited knowledge in immunological manipulation and
the adverse effects that happened, further VCA cases were put on hold. It was not until the discovery and
development of cyclosporin A during kidney transplantation that it was applied to VCA in the 1980s where
immunosuppression finally became more effective. The first successful hand transplant then was carried out
in 1998 in France. However, the patient refused to adhere to the immunosuppressive regimen due to personal
reasons and compliance issues and hence the arm was again amputated almost 3 years after surgery. The
[4]
first vascularized tendons were performed by Guimberteau et al. where two allotransplantations of digital
flexor tendon apparatus were collected from a living nonrelated donor and from a deceased donor. The
tendons were then revascularized using the recipient’s ulna vessels and ultimately received acceptable using
multiple doses of cyclosporin A . The first successful face transplant occurred in 2005 and since then,
[5]
[6]
several countries have followed suit.
An overview of clinical VCA cases to date
Only a few specialized centers in the world with the capability and infrastructure for performing a VCA
procedure. As such, an important source of data is the International Registry on Hand and Composite
Tissue Transplantation (IRHCTT), which is a voluntary registry that collects clinical information on VCAs.
The most recent report of the IRHCTT was published in 2010 and provides follow-up data on 49 hand
transplants in 33 patients. Thus far, there have been 89 hand transplants performed since 1998. The United
States currently has the largest number of cases, followed by China and Poland.

TYPES OF VCA ANIMAL MODELS REPORTED
Face transplant models
A variety of animal models have been used in VCA experiments with the majority being orthotopic face
transplants. The animal models were performed in animals such as primates, swine, sheep, canine, rabbit,
rats and mice. Different compositions of face allograft comprising of bone, nerve and soft tissue in each
animal model have been reported in the literature which has varying levels of antigenicity. As such, each
report has used varying types of immunosuppression, which is also dependent on the response of each
animal type and to the type of immunosuppressive drug. The transplantation of each allograft can be
considered orthotopic if the graft replaces the original site of the donor, i.e., the face, or heterotopic if the
allograft is placed in a distant site different from the original area. Orthotopic transplants in these animal
models are mostly for assessing not only the rejection process but also the functional restoration of the
allograft. Heterotopic allografts, however, are used more for assessing the degree of rejection but normally
do not carry an assessment of functional recovery.

In a primate model, heterotopic transfer of a facial transplant including the mandible was transferred from
MHC mismatched M fascicularis monkeys. Anti-thymocyte globulin (ATG) was used as an induction
regimen with tacrolimus and rapamycin in combination as a maintenance regimen.

Two reports using swine and sheep models were used with facial allografts including bone. However, no
immunosuppression was used in these models and was more for the surgical technique of producing such
models.

Four canine models were used in mismatched donors to beagle dog recipients. All reports were orthotopic
and involved a hemifacial transplantation. With these reports, 2 reports utilized cyclosporine and steroids as
maintenance immunosuppression. Two other reports used tacrolimus as maintenance immunosuppression
and with 1 report using tacrolimus only for 7 days. One report in a rabbit model used a face and scalp
transplantation model with no immunosuppression.