Imran Ullah1, Ran Lee1, Keon Bong Oh1, Youngim Kim1, Jae-Seok Woo1, Seongsoo Hwang1, Gi-Sun Im1, Sun A Ock2. 1. Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea. 2. Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea. Electronic address: ocksamoon@gmail.com.
Abstract
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 RT2 Profiler PCR array and whole blood samples from GalTKO/hCD46 Massachusetts General Hospital (MGH) pigs. 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: 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: 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.
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 humanmembrane 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 RT2 Profiler PCR array and whole blood samples from GalTKO/hCD46 Massachusetts General Hospital (MGH) pigs. 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: 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: 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.