Isolation outcome and functional characteristics of young and adult pig pancreatic islets for transplantation studies.
BACKGROUND
Pig islets have been proposed as an alternative to human islets for clinical use, but their use is limited by rejection. The availability of genetically modified pigs devoid of alpha1,3-galactosyltransferase might provide islets more suitable for xenotransplantation. To limit the costs involved in the logistics and health care of pigs for clinical xenotransplantation, we have studied whether younger, rather than older, pigs that are typically preferred can be used as islet donors.


METHODS
We utilized pancreases from Yorkshire and White Landrace wild-type pigs and alpha1,3-galactosyltransferase gene-knockout pigs of three main different age and size groups: (i) <6 months, (ii) 6 to 12 months, and (iii) >2 yr of age, inclusive of retired breeders. We compared isolation yield and in vitro and in vivo function of islet cells obtained from these groups.


RESULTS
Islets from adult pigs (>2 yr) offered not only higher islet yields, but retained the ability to preserve intact morphology during the isolation process and culture, in association with high functional properties after transplantation. Following isolation, islet cells from young (<6 m) and young-adult (6 to 12 m) pigs dissociated into small aggregates and single cells, and exhibited inferior functional properties than adult islets both in vitro and in vivo.


CONCLUSIONS
These data support the conclusion that, in view of the large number of islets needed to maintain normoglycemia after xenotransplantation, organ-source pigs need to reach adult age (>2 yr) before being considered optimal islet donors, in spite of the higher costs involved.
Bottino
Rita
R
Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, Rangos Research Center, Pittsburgh, PA 15213, USA. rib16@pitt.edu
Balamurugan
A N
AN
Smetanka
Cynthia
C
Bertera
Suzanne
S
He
Jing
J
Rood
Pleunie P M
PP
Cooper
David K C
DK
Trucco
Massimo
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D048430:Cell Shape; D002478:Cells, Cultured; D006085:Graft Survival; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism / Q000601:surgery*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D013552:Swine; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D001786:Blood Glucose; D007328:Insulin