Seven Years of Experiences of Preclinical Experiments of Xeno-Heart Transplantation of Pig to Non-Human Primate (Cynomolgus Monkey)

Lee, S.J.; Kim, J.S.; Chee, Hyun Keun; Yun, Ik Jin; Park, K.S.; Yang, Hyun Suk; Park, J.H.

doi:10.1016/j.transproceed.2018.01.041

Cited by 16 publications

(14 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The GTKO pig heart had an average growth rate of $5.4 g/kg body weight increase. Similar heart growth rates (5.3-5.6 g/kg body weight) have been observed in qualified pathogen-free (QPF) pigs, 9 GTKO pigs 5 and GTKO-CD46 pigs, 5 suggesting that body weight is a trustworthy physical parameter to estimate heart size.…”

Section: Resultssupporting

confidence: 58%

“…Non-human primates (NHPs) transplanted with GTKO pig hearts or kidneys survived for several days, and with additional gene modifications and advancements in immune suppression, xenograft survival now greatly increased and can be achieved beyond two years. 3–7 Physical parameters such as size, weight and morphology also have a substantial impact on the functionality as well as the success of cardiac and renal graft transplantation. However, the literature on the morphometries of the GTKO pig is scarce.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Morphometric analysis of alpha-1, 3-galactosyltransferase knockout pig kidney and heart

et al. 2020

View full text Add to dashboard Cite

We report a morphometric evaluation of α1,3-galactosyltransferase knockout (GTKO) pig heart and kidney ( n = 9) at the end of one, three and seven months. Organs parameters gradually increased with the age ( p < 0.05) and body weight ( p < 0.05) of the pigs. Organs morphometries were significantly correlated to the age and body weight of the animal. We were able to conclude the average size of GTKO pig heart and kidney based on age and body weight, which could be helpful in estimating the size of these organs non-invasively for transplantation.

show abstract

Section: Resultssupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Morphometric analysis of alpha-1, 3-galactosyltransferase knockout pig kidney and heart

et al. 2020

View full text Add to dashboard Cite

show abstract

“…This subject choice was necessary, as only humans and non‐human primates possess preformed antibodies to the α‐1,3‐galactose porcine epitope, and thus reject wild‐type porcine tissues in a similar manner 30,31 . Furthermore, cynomolgus monkeys are well established in previous literature as scientifically appropriate subjects for such studies 32,33 . Non‐naïve animals were included as recipients in this study due to limited subject availability and to most ethically and prudently steward the use of research animals.…”

Section: Methodsmentioning

confidence: 99%

“…30,31 Furthermore, cynomolgus monkeys are well established in previous literature as scientifically appropriate subjects for such studies. 32,33 Non-naïve animals were included as recipients in this study due to limited subject availability and to most ethically and prudently steward the use of research animals. These animals had previously been involved in pharmacokinetic studies that involved administration of drugs intended to reduce relapsed alcohol consumption and for treatment of cocaine abuse.…”

Section: Xenotransplant Recipientsmentioning

confidence: 99%

Immunological response in cynomolgus macaques to porcine α‐1,3 galactosyltransferase knockout viable skin xenotransplants—A pre‐clinical study

Holzer¹,

Chang²,

Wicks³

et al. 2020

Xenotransplantation

View full text Add to dashboard Cite

Background: Allogeneic skin recovered from human deceased donors (HDD) has been a mainstay interim treatment for severe burns, but unfortunately risk of infectious disease and availability limitations exist. Genetically engineered ɑ-1,3 galactosyltransferase knockout (GalT-KO) porcine source animals for viable skin xenotransplants may provide a promising clinical alternative. Methods: Four cynomolgus macaque recipients received full-thickness surgical wounds to model the defects arising from excision of full-thickness burn injury and were treated with biologically active skin xenotransplants derived from GalT-KO, Designated Pathogen Free (DPF) miniature swine. Evaluations were conducted for safety, tolerability, and recipient immunological response. Results: All skin xenotransplants demonstrated prolonged survival, vascularity, and persistent dermal adhesion until the study endpoint at post-operative day 30. No adverse outcomes were observed during the study. Varying levels of epidermolysis coincided with histologic detection of CD4+ and CD8+ T cells, and other cellular infiltrates in the epidermis. Recipient sera IgM and IgG demonstrated significant antibody immune response to non-α-1,3-galactose porcine xenoantigens. Separately, specific wound healing mediators were quantified. Neither porcine cell migration nor PERV were detected in circulation or any visceral organs. Conclusions: These results provide a detailed analysis of vital skin xenotransplants utilizing a non-human primate model to predict the anticipated immunological response of human patients. The lack of adverse rejection even in the presence of elevated Ig indicates this is a prospective therapeutic option. The findings reported here directly supported regulatory clearance for a first-in-man, Phase I xenotransplantation clinical trial.

show abstract

“…According to previous studies, pigs have specific physiological similarities to humans [12]. Among the other transgenic animals that have been produced, the transgenic pig is particularly useful in xenotransplantation [13], treatment of human diseases [14], and therapeutic protein production. Moreover, transgenic pigs have been used in bioreactors [15] and agricultural industries, as well as in studies aimed at enhancing the meat quality and quantity [16].…”

Section: Introductionmentioning

confidence: 99%

Improved preimplantation development of porcine somatic cell nuclear transfer embryos by caffeine treatment

et al. 2019

View full text Add to dashboard Cite

This study examined the effects of a caffeine treatment to improve nuclear reprogramming in porcine cloned embryos. Embryonic development and the expression of genes related to pluripotency ( POU5F1 , SOX2 , NANOG , and CDX2 ) were compared after caffeine supplementation during manipulation at different concentrations (0, 1.25, 2.5, and 5.0 mM) and after varying the delayed activation time (control, 1, 2, and 4 h) after fusion. Caffeine added to media during manipulation produced a higher rate of development to blastocysts in the 1.25 mM group than in the other concentration groups (22.8% vs. 16.1%, 16.2%, and 19.2%; p < 0.05). When caffeine was added during the 4 h delayed activation, the 1.25 mM caffeine concentration produced a significantly higher rate of development than those in the other 4 h-activation-delayed caffeine concentration groups (22.4% vs. 9.4%, 14.0%, and 11.1%; p < 0.05). On the other hand, no significant improvement over that in the control group was observed when caffeine was supplemented during both the manipulation period and delayed activation period (16.0% vs. 15.2%), respectively. The levels of POU5F1 , SOX2 , and NANOG expression in blastocysts were significantly higher in the delayed activation caffeine group (4 h, 1.25 mM) than in the control group (1 h, 0 mM; p < 0.05). In conclusion, a caffeine treatment at 1.25 mM during delayed activation for 4 h can improve the preimplantation development of porcine somatic cell nuclear transfer embryos by activating nuclear reprogramming.

show abstract

Seven Years of Experiences of Preclinical Experiments of Xeno-Heart Transplantation of Pig to Non-Human Primate (Cynomolgus Monkey)

Cited by 16 publications

References 12 publications

Morphometric analysis of alpha-1, 3-galactosyltransferase knockout pig kidney and heart

Morphometric analysis of alpha-1, 3-galactosyltransferase knockout pig kidney and heart

Immunological response in cynomolgus macaques to porcine α‐1,3 galactosyltransferase knockout viable skin xenotransplants—A pre‐clinical study

Improved preimplantation development of porcine somatic cell nuclear transfer embryos by caffeine treatment

Contact Info

Product

Resources

About