Isolation outcome and functional characteristics of young and adult pig pancreatic islets for transplantation studies

被引:72
作者
Bottino, Rita
Balamurugan, A. N.
Smetanka, Cynthia
Bertera, Suzanne
He, Jing
Rood, Pleunie P. M.
Cooper, David K. C.
Trucco, Massimo
机构
[1] Childrens Hosp Pittsburgh, Rangos Res Ctr, Dept Pediat, Divv Immunogenet, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15260 USA
关键词
porcine islets; retired breeder donor pigs; young donor pigs;
D O I
10.1111/j.1399-3089.2006.00374.X
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 alpha 1,3-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 alpha 1,3-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.
引用
收藏
页码:74 / 82
页数:9
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