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Open AccessArticle

Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms

1
Department of Animal Science and Technology, College of Biotechnology and Natural Resources, Chung-Ang University, Gyeonggi-do 17546, Korea
2
Animal Biotechnology Division, National Institute of Animal Science, RDA, Jeollabukdo 55365, Korea
3
Departments of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea
4
Department of Laboratory Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Dongan-gu, Anyang 14068, Korea
5
Primate Organ Transplantation Centre, Genia Inc., Sungnam 13201, Korea
6
Departments of Thoracic and Cardiovascular Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea
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Departments of Nephrology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea
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Departments of Cardiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea
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Departments of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea
*
Authors to whom correspondence should be addressed.
Equal contribution.
Int. J. Mol. Sci. 2021, 22(2), 751; https://doi.org/10.3390/ijms22020751
Received: 18 December 2020 / Revised: 5 January 2021 / Accepted: 11 January 2021 / Published: 13 January 2021
(This article belongs to the Special Issue Epigenetic Mechanisms of Cardiac Disease)
Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old alpha-1,3-galactosyltransferase knockout (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation). The recipient monkey’s blood parameters were analyzed on days −7, −3, 1, 4, and 7. Validation was conducted by quantitative real-time PCR (qPCR) with selected genes. A non-transplanted GTKO porcine heart from an age-matched litter was used as a control. The recipient monkey showed systemic inflammatory responses, and the rejected cardiac graft indicated myocardial infarction and cardiac fibrosis. The transplanted heart exhibited a total of 3748 differentially expressed genes compared to the non-transplanted heart transcriptome, with 2443 upregulated and 1305 downregulated genes. Key biological pathways involved at the terminal stage of graft rejection were cardiomyopathies, extracellular interactions, and ion channel activities. The results of qPCR evaluation were in agreement with the transcriptome data. Transcriptome analysis of porcine cardiac tissue at graft rejection reveals dysregulation of the key molecules and signaling pathways, which play relevant roles on structural and functional integrities of the heart. View Full-Text
Keywords: porcine cardiac tissue; Xenotransplatation; heart failure; transcriptome analysis (or RNA-seq analysis) porcine cardiac tissue; Xenotransplatation; heart failure; transcriptome analysis (or RNA-seq analysis)
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MDPI and ACS Style

Park, M.Y.; Krishna Vasamsetti, B.M.; Kim, W.S.; Kang, H.J.; Kim, D.-Y.; Lim, B.; Cho, K.; Kim, J.S.; Chee, H.K.; Park, J.H.; Yang, H.S.; Rallabandi, H.R.; Ock, S.A.; Park, M.-R.; Lee, H.; Hwang, I.-S.; Kim, J.-M.; Oh, K.B.; Yun, I.J. Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms. Int. J. Mol. Sci. 2021, 22, 751. https://doi.org/10.3390/ijms22020751

AMA Style

Park MY, Krishna Vasamsetti BM, Kim WS, Kang HJ, Kim D-Y, Lim B, Cho K, Kim JS, Chee HK, Park JH, Yang HS, Rallabandi HR, Ock SA, Park M-R, Lee H, Hwang I-S, Kim J-M, Oh KB, Yun IJ. Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms. International Journal of Molecular Sciences. 2021; 22(2):751. https://doi.org/10.3390/ijms22020751

Chicago/Turabian Style

Park, Min Y.; Krishna Vasamsetti, Bala M.; Kim, Wan S.; Kang, Hee J.; Kim, Do-Young; Lim, Byeonghwi; Cho, Kahee; Kim, Jun S.; Chee, Hyun K.; Park, Jung H.; Yang, Hyun S.; Rallabandi, Harikrishna R.; Ock, Sun A.; Park, Mi-Ryung; Lee, Heasun; Hwang, In-Sul; Kim, Jun-Mo; Oh, Keon B.; Yun, Ik J. 2021. "Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms" Int. J. Mol. Sci. 22, no. 2: 751. https://doi.org/10.3390/ijms22020751

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