Stable Regulation of Senescence-Related Genes in Galactose-alpha1,3-galactose Epitope Knockout and Human Membrane Cofactor Protein hCD46 Pig.
Aging
/ genetics
Animals
Animals, Genetically Modified
Child, Preschool
Disease Models, Animal
Epitopes
Galactose
/ deficiency
Galactosyltransferases
/ genetics
Gene Knockout Techniques
Graft Survival
/ immunology
Heterografts
Humans
Membrane Cofactor Protein
/ genetics
Middle Aged
Swine
Swine, Miniature
Transplantation, Heterologous
/ methods
Journal
Transplantation proceedings
ISSN: 1873-2623
Titre abrégé: Transplant Proc
Pays: United States
ID NLM: 0243532
Informations de publication
Date de publication:
Historique:
received:
07
01
2019
revised:
19
02
2019
accepted:
13
03
2019
entrez:
11
8
2019
pubmed:
11
8
2019
medline:
19
11
2019
Statut:
ppublish
Résumé
Pigs are considered suitable animal donor models for xenotransplantation. For successful organ transplantation, immune rejection must be overcome. Xenotransplantation has recently been successfully performed using galactose-alpha1,3-galactose epitopes knockout (GalTKO) and a human membrane cofactor protein (hCD46) in a pig model. However, the growth and lifespan of the grafted organ have not been evaluated. Therefore, in the present study we evaluated aging and 84 senescence-related genes using the RT Experimental groups were double GalTKO/hCD46 (5-month-old), single GalTKO/hCD46 (2-year-old), and non-genetically modified (>3.5-year-old; control group within the same strain). Age-matched white hairless Yucatan (WHY) miniature pig groups were used as controls. Among the 19 senescence-related genes selected from the 84 genes for further evaluation, 13 were upregulated in the double GalTKO/hCD46 MGH pigs compared to control MGH pigs; however, in WHY pigs, only 4 genes were up- or down-regulated among the 19 genes. Moreover, in double GalTKO/hCD46 MGH and WHY pigs, the expression of the 19 genes changed only 1- to 2-fold, suggesting that there were no significant differences in senescence signals between the 2 pig lines. The present results indicate that the double GalTKO/hCD46 MGH pig might be a suitable model for human xenotransplantation studies. However, we used a limited number of experimental individuals, so further studies using larger experimental groups should be conducted to verify the present results.
Sections du résumé
BACKGROUND
BACKGROUND
Pigs are considered suitable animal donor models for xenotransplantation. For successful organ transplantation, immune rejection must be overcome. Xenotransplantation has recently been successfully performed using galactose-alpha1,3-galactose epitopes knockout (GalTKO) and a human membrane cofactor protein (hCD46) in a pig model. However, the growth and lifespan of the grafted organ have not been evaluated. Therefore, in the present study we evaluated aging and 84 senescence-related genes using the RT
METHODS
METHODS
Experimental groups were double GalTKO/hCD46 (5-month-old), single GalTKO/hCD46 (2-year-old), and non-genetically modified (>3.5-year-old; control group within the same strain). Age-matched white hairless Yucatan (WHY) miniature pig groups were used as controls.
RESULTS
RESULTS
Among the 19 senescence-related genes selected from the 84 genes for further evaluation, 13 were upregulated in the double GalTKO/hCD46 MGH pigs compared to control MGH pigs; however, in WHY pigs, only 4 genes were up- or down-regulated among the 19 genes. Moreover, in double GalTKO/hCD46 MGH and WHY pigs, the expression of the 19 genes changed only 1- to 2-fold, suggesting that there were no significant differences in senescence signals between the 2 pig lines.
CONCLUSIONS
CONCLUSIONS
The present results indicate that the double GalTKO/hCD46 MGH pig might be a suitable model for human xenotransplantation studies. However, we used a limited number of experimental individuals, so further studies using larger experimental groups should be conducted to verify the present results.
Identifiants
pubmed: 31399182
pii: S0041-1345(19)30046-6
doi: 10.1016/j.transproceed.2019.03.028
pii:
doi:
Substances chimiques
CD46 protein, human
0
Epitopes
0
Membrane Cofactor Protein
0
Galactosyltransferases
EC 2.4.1.-
Galactose
X2RN3Q8DNE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2043-2050Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.