Biomedical Engineering Reference
In-Depth Information
Chapter 16
Xenotransplantation
David K.C. Cooper
*
and Robert Wagner
y
*
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA,
y
Division of Laboratory Animal Resources,
University of Pittsburgh, Pittsburgh, PA, USA
Chapter Outline
Introduction
391
Intravascular Catheter Placement and Fluid/Drug
Administration
The Pig as a Potential Source of Organs/Cells for Clinical
Transplantation
393
391
Immunosuppressive Therapy
396
The Significance of Gal Antigen Expression in Pigs
391
Results and Complications
397
History
392
Results
397
Pathobiology of Pig-To-Primate Organ Transplantation
393
Complications
397
The Innate Immune Response
393
Genetic Modification of Pigs
399
Coagulation Dysfunction
393
Summary
400
The Adaptive Immune Response
393
Acknowledgments
400
The Pig-to-Nonhuman Primate Model
393
References
400
INTRODUCTION
Organ allotransplantation (alloTx) for patients with end-
stage organ failure was one of the success stories of the
second half of the twentieth century. One of the major
limitations of this form of surgical therapy is the shortage
of suitable donor organs, which are largely from deceased
humans. Furthermore, during the past decade, islet alloTx
for the treatment of type 1 diabetes has become moderately
successful, but the shortage of suitable pancreata from
deceased humans has limited this form of therapy to less
than 1000 of the estimated 2 million type 1 diabetics in the
USA during the past decade. In an effort to resolve the
problem of shortage of organs and cells, increasing atten-
tion has been directed towards an exploration of the use
of animals as potential sources of tissues for clinical
transplantation.
species, e.g., monkey-to-baboon, are those in which,
following an organ transplant, hyperacute rejection does
not commonly occur, whereas discordant species, e.g. pig-
to-baboon, are those in which hyperacute rejection is
almost universal. Despite the problem of hyperacute
rejection, for a number of logistic and ethical reasons
(reviewed in
Cooper and Lanza, 2000
and
Cooper et al.,
2002
)(
Table 16.1
), the pig has been determined to be the
most suitable source of such organs, tissues, or cells for
clinical use. Almost all research of direct clinical relevance
today is being carried out in pig-to-nonhuman primate
models, although in vitro and small animal studies continue
to play important roles in providing initial data.
The Significance of Gal Antigen Expression
in Pigs
Studies in the 1990s determined that, when the recipient
was a nonhuman primate or human, hyperacute rejection
was largely related to the expression in pigs of a carbohy-
drate antigen, Gal
The Pig as a Potential Source of Organs/
Cells for Clinical Transplantation
Xenotransplantation (xenoTx), or the transplantation of
organs, tissues, or cells across species barriers, has some-
times been divided into the transplantation of organs
between concordant or discordant species. Concordant
1,3Gal (Gal) (
Cooper, 1992; Cooper
et al., 1993; Oriol et al., 1993
), which is not present in Old
World nonhuman primates and humans (
Galili, 1988
). As
a result of its absence in these species, they develop natural
a
