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107. Acetyl‐CoA carboxylase‐1/2 blockade locks dendritic cells in the semimature state associated with FA deprivation by favoring FAO.

Author

Nguyen‐Phuong, Thuy, Chung, Hyunwoo, Jang, Jiyun, Kim, Jung‐Sik, and Park, Chung‐Gyu

Subjects
DENDRITIC cells, ACETYLCOENZYME A, CELL respiration, FATTY acid oxidation, CARBOXYLASES
Abstract

Immunometabolism is rising as an intriguing topic that reveals the connection between immune cell function and metabolic processes. Especially, fatty acid metabolism plays an essential role in the dendritic cells (DCs) during the differentiation and maturation period. We questioned whether regulation of acetyl‐CoA carboxylases 1 and 2‐(ACC1/2), the core enzymes of fatty acid synthesis (FAS), would control DC function. Here, we report that blocking ACC1/2 to prevent FAS during DC maturation switched their cellular metabolism into fatty acid oxidation to fuel oxidative phosphorylation. This action turned DCs to utilize exogenous fatty acids to sustain their basal energy demand and maintain a stable cellular respiration rate. Coincidentally, under the ACC1/2 inhibitor treatment, LPS‐treated DCs exhibited a semimaturation phenotype with a maturation‐resistance feature, with decreased expression of costimulatory molecules including CD86 and CD40, along with the reduction of IL‐12 and IL‐6. The migratory capability of DCs has been known to relate to the glycolysis pathway, and here we showed that the ACC1/2 blockade did not affect the expression of CCR7 and DC migration. Furthermore, we found that under the ACC1/2 blocking condition, DCs pulsed with OVA failed to activate OVA‐specific CD4+ T cell proliferation even though their antigen uptake capacity was intact. Together, our data suggest ACC1/2 as a promising target to control DC fate. [ABSTRACT FROM AUTHOR]

Published
2022
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116. Improved efficiencies in the generation of multigene-modified pigs by recloning and using sows as the recipient.

Author

Cho, Jongki, Kim, Ghangyong, Qamar, Ahmad Yar, Fang, Xun, Roy, Pantu Kumar, Tanga, Bereket Molla, Bang, Seonggyu, Kim, Jong Keun, Galli, Cesare, Perota, Andrea, Kim, Young Tae, Che, Jeong-Hwan, and Park, Chung-Gyu

Subjects
SWINE, SOWS, PROTEIN C, EMBRYO transfer, PROTEIN receptors
Abstract

Summary: This study was performed to improve production efficiency at the level of recipient pig and donor nuclei of transgenic cloned pigs used for xenotransplantation. To generate transgenic pigs, human endothelial protein C receptor (hEPCR) and human thrombomodulin (hTM) genes were introduced using the F2A expression vector into GalT–/–/hCD55+ porcine neonatal ear fibroblasts used as donor cells and cloned embryos were transferred to the sows and gilts. Cloned fetal kidney cells were also used as donor cells for recloning to increase production efficiency. Pregnancy and parturition rates after embryo transfer and preimplantation developmental competence were compared between cloned embryos derived from adult and fetal cells. Significantly higher parturition rates were shown in the group of sows (50.0 vs. 4.1%), natural oestrus (20.8 vs. 0%), and ovulated ovary (16.7 vs. 5.6%) compared with gilt, induced and non-ovulated, respectively (P < 0.05). When using gilts as recipients, final parturitions occurred in only the fetal cell groups and significantly higher blastocyst rates (15.1% vs. 21.3%) were seen (P < 0.05). Additionally, gene expression levels related to pluripotency were significantly higher in the fetal cell group (P < 0.05). In conclusion, sows can be recommended as recipients due to their higher efficiency in the generation of transgenic cloned pigs and cloned fetal cells also can be recommended as donor cells through correct nuclear reprogramming. [ABSTRACT FROM AUTHOR]

Published
2022
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117. Multiple biomarkers study in painters in a shipyard in Korea

Author

Lee, Kyoung-Ho, Ichiba, Masayoshi, Zhang, Jiusong, Tomokuni, Katsumaro, Hong, Yun-Chul, Ha, Mina, Kwon, Ho Jang, Koh, Sang-Back, Choi, Hong-Ryul, Lee, Kwan-Hee, Park, Chung-Gyu, Cho, Soo-Hun, Hirvonen, Ari, Strickland, Paul T, Vermeulen, Roel, Hayes, Richard B, and Kang, Daehee

Published
2003
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119. 'The 2018 Changsha Communiqué' The 10-Year Anniversary of The International Consultation on Xenotransplantation

Author

Hawthorne, Wayne J., Cowan, Peter J., Bühler, Léo H., Yi, Shounan, Bottino, Rita, Pierson, Richard N. III, Ahn, Curie, Azimzadeh, Agnes, Cozzi, Emanuele, Gianello, Pierre, Lakey, Jonathan R.T., Luo, Minhua, Miyagawa, Shuji, Mohiuddin, Muhammad M., Park, Chung-Gyu, Schuurman, Henk-Jan, Scobie, Linda, Sykes, Megan, Tector, Joseph, Tönjes, Ralf Reinhard, Wolf, Eckard, Nunez, José R., Wang, Wei, Third WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, and UCL - (SLuc) Service de chirurgie et transplantation abdominale

Published
2019

123. Bioinformatic analysis of peripheral blood RNA-sequencing sensitively detects the cause of late graft loss following overt hyperglycemia in pig-to-nonhuman primate islet xenotransplantation

Author

Kim, Hyun-Je, primary, Moon, Ji Hwan, additional, Chung, Hyunwoo, additional, Shin, Jun-Seop, additional, Kim, Bongi, additional, Kim, Jong-Min, additional, Kim, Jung-Sik, additional, Yoon, Il-Hee, additional, Min, Byoung-Hoon, additional, Kang, Seong-Jun, additional, Kim, Yong-Hee, additional, Jo, Kyuri, additional, Choi, Joungmin, additional, Chae, Heejoon, additional, Lee, Won-Woo, additional, Kim, Sun, additional, and Park, Chung-Gyu, additional

Published
2019
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125. Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates

Author

Yoon, Chang Ho, primary, Choi, Se Hyun, additional, Choi, Hyuk Jin, additional, Lee, Hyun Ju, additional, Kang, Hee Jung, additional, Kim, Jong Min, additional, Park, Chung‐Gyu, additional, Choi, Kimyung, additional, Kim, Hyunil, additional, Ahn, Curie, additional, and Kim, Mee Kum, additional

Published
2019
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130. ThirdWHOGlobal Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials, Changsha, Hunan, China December 12–14, 2018

Author

Hawthorne, Wayne J., primary, Cowan, Peter J., additional, Bühler, Léo H., additional, Yi, Shounan, additional, Bottino, Rita, additional, Pierson, Richard N., additional, Ahn, Curie, additional, Azimzadeh, Agnes, additional, Cozzi, Emanuele, additional, Gianello, Pierre, additional, Lakey, Jonathan R. T., additional, Luo, Minhua, additional, Miyagawa, Shuji, additional, Mohiuddin, Muhammad M., additional, Park, Chung‐Gyu, additional, Schuurman, Henk‐Jan, additional, Scobie, Linda, additional, Sykes, Megan, additional, Tector, Joseph, additional, Tönjes, Ralf Reinhard, additional, Wolf, Eckhard, additional, Nuñez, José R., additional, and Wang, Wei, additional

Published
2019
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131. Cover Image, Volume 26, Issue 2

Author

Hawthorne, Wayne J., primary, Cowan, Peter J., additional, Bühler, Léo H., additional, Yi, Shounan, additional, Bottino, Rita, additional, Pierson, Richard N., additional, Ahn, Curie, additional, Azimzadeh, Agnes, additional, Cozzi, Emanuele, additional, Gianello, Pierre, additional, Lakey, Jonathan R. T., additional, Luo, Minhua, additional, Miyagawa, Shuji, additional, Mohiuddin, Muhammad M., additional, Park, Chung‐Gyu, additional, Schuurman, Henk‐Jan, additional, Scobie, Linda, additional, Sykes, Megan, additional, Tector, Joseph, additional, Tönjes, Ralf Reinhard, additional, Wolf, Eckhard, additional, Nuñez, José R., additional, and Wang, Wei, additional

Published
2019
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133. Third WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials, Changsha, Hunan, China December 12-14, 2018: 'The 2018 Changsha Communiqué' The 10-Year Anniversary of The International Consultation on Xenotransplantation.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Hawthorne, Wayne J, Cowan, Peter J, Bühler, Léo H, Yi, Shounan, Bottino, Rita, Pierson, Richard N, Ahn, Curie, Azimzadeh, Agnes, Cozzi, Emanuele, Gianello, Pierre, Lakey, Jonathan R T, Luo, Minhua, Miyagawa, Shuji, Mohiuddin, Muhammad M, Park, Chung-Gyu, Schuurman, Henk-Jan, Scobie, Linda, Sykes, Megan, Tector, Joseph, Tönjes, Ralf Reinhard, Wolf, Eckhard, Nuñez, José R, Wang, Wei, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Hawthorne, Wayne J, Cowan, Peter J, Bühler, Léo H, Yi, Shounan, Bottino, Rita, Pierson, Richard N, Ahn, Curie, Azimzadeh, Agnes, Cozzi, Emanuele, Gianello, Pierre, Lakey, Jonathan R T, Luo, Minhua, Miyagawa, Shuji, Mohiuddin, Muhammad M, Park, Chung-Gyu, Schuurman, Henk-Jan, Scobie, Linda, Sykes, Megan, Tector, Joseph, Tönjes, Ralf Reinhard, Wolf, Eckhard, Nuñez, José R, and Wang, Wei

Abstract

After feedback from the working parties, the final session focused on drafting proposed revisions of the WHO documents, and resulted in the formulation of the draft “Third WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials, The 2018 Changsha Communiqué.” This draft was submitted to WHO in February 2019 for WHO and World Health Assembly consideration. If approved, the 2018 Changsha Communiqué will then be posted on the websites of WHO, IXA, and TTS, and published in Xenotransplantation. This report includes summaries of the various sessions, followed by the abstracts of invited speakers from the update sessions.

Published
2019

134. 'The 2018 Changsha Communiqué' The 10-Year Anniversary of The International Consultation on Xenotransplantation.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Hawthorne, Wayne J., Cowan, Peter J., Bühler, Léo H., Yi, Shounan, Bottino, Rita, Pierson, Richard N. III, Ahn, Curie, Azimzadeh, Agnes, Cozzi, Emanuele, Gianello, Pierre, Lakey, Jonathan R.T., Luo, Minhua, Miyagawa, Shuji, Mohiuddin, Muhammad M., Park, Chung-Gyu, Schuurman, Henk-Jan, Scobie, Linda, Sykes, Megan, Tector, Joseph, Tönjes, Ralf Reinhard, Wolf, Eckard, Nunez, José R., Wang, Wei, Third WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Hawthorne, Wayne J., Cowan, Peter J., Bühler, Léo H., Yi, Shounan, Bottino, Rita, Pierson, Richard N. III, Ahn, Curie, Azimzadeh, Agnes, Cozzi, Emanuele, Gianello, Pierre, Lakey, Jonathan R.T., Luo, Minhua, Miyagawa, Shuji, Mohiuddin, Muhammad M., Park, Chung-Gyu, Schuurman, Henk-Jan, Scobie, Linda, Sykes, Megan, Tector, Joseph, Tönjes, Ralf Reinhard, Wolf, Eckard, Nunez, José R., Wang, Wei, and Third WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials

Published
2019

135. Long‐term porcine islet graft survival in diabetic non‐human primates treated with clinically available immunosuppressants.

Author

Kim, Jong‐Min, Hong, So‐Hee, Chung, Hyunwoo, Shin, Jun‐Seop, Min, Byoung‐Hoon, Kim, Hyun Je, Kim, Jiyeon, Hwang, Eung Soo, Kang, Hee‐Jung, Ha, Jongwon, and Park, Chung‐Gyu

Subjects
TYPE 1 diabetes, IMMUNOSUPPRESSIVE agents, PRIMATES, ISLANDS of Langerhans, CIRCOVIRUS diseases, GRAFT survival
Abstract

Background: Although pancreatic islet transplantation is becoming an effective therapeutic option for patients with type 1 diabetes (T1D) who suffer from a substantially impaired awareness of hypoglycemia, its application is limited due to the lack of donors. Thus, pig‐to‐human islet xenotransplantation has been regarded as a promising alternative due to the unlimited number of "donor organs." Long‐term xenogeneic islet graft survival in pig‐to‐non‐human primate (NHP) models has mainly been achieved by administering the anti‐CD154 mAb‐based immunosuppressant regimen. Since the anti‐CD154 mAb treatment has been associated with unexpected fatal thromboembolic complications in clinical trials, the establishment of a new immunosuppressant regimen that is able to be directly applied in clinical trials is an urgent need. Methods: We assessed an immunosuppressant regimen composed of clinically available agents at porcine islet transplantation in consecutive diabetic NHPs. Results: Porcine islet graft survival in consecutive diabetic NHPs (n = 7; >222, >200, 181, 89, 62, 55, and 34 days) without severe adverse events. Conclusion: We believe that our study could contribute greatly to the initiation of islet xenotransplantation clinical trials. [ABSTRACT FROM AUTHOR]

Published
2021
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139. CD4+/CD8+ T‐cell ratio correlates with the graft fate in pig‐to‐non‐human primate islet xenotransplantation.

Author

Chung, Hyunwoo, Kim, Hyun‐Je, Kim, Jung‐Sik, Yoon, Il‐Hee, Min, Byoung‐Hoon, Shin, Jun‐Seop, Kim, Jong‐Min, Lee, Won‐Woo, and Park, Chung‐Gyu

Subjects
XENOTRANSPLANTATION, ISLANDS of Langerhans, RHESUS monkeys, PRIMATES, T cells
Abstract

Background: Xenogeneic islet transplantation using porcine pancreata has been a promising option for substituting human islet transplantation. Moreover, recent advances in pre‐clinical results have put islet xenotransplantation closer to the possibility of clinical application. While preparing for the era of clinical xenotransplantation, developing non‐invasive immune monitoring method which could predict the graft fate could benefit the patient. However, there are few reports showing predictive immune parameters associated with the fate of the graft in islet xenotransplantation. Methods: The absolute number and ratio of T‐cell subsets have been measured via flow cytometry from the peripheral blood of 16 rhesus monkeys before and after porcine islet xenotransplantation. The correlation between the graft survival and the absolute number or ratio of T cells was retrospectively analyzed. Results: The ratio of CD4+ versus CD8+ T cells was significantly reduced due to CD8+ effector memory cells' increase. Correlation analyses revealed that CD4+/CD8+, CD4+/CD8+ naïve, CD4+ naïve/CD8+ naïve, and CD4+ central memory/CD8+ naïve cell ratios negatively correlated with the duration of graft survival. Conversely, further analyses discovered strong, positive correlation of CD4+/CD8+ cell ratios within the early graft‐rejected monkeys (≤60 days). Conclusions: This retrospective study demonstrated that CD4+/CD8+ ratios correlated with graft survival, especially in recipients which rejected the graft in early post‐transplantation periods. CD4+/CD8+ ratios could be used as a surrogate marker to predict the graft fate in pig‐to‐NHP islet xenotransplantation. [ABSTRACT FROM AUTHOR]

Published
2020
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141. Ascites formation accompanied by portal vein thrombosis after porcine islet xenotransplantation via the portal vein in Rhesus macaque (Macaca mulatta )

Author

Kim, Jong-Min, primary, Shin, Jun-Seop, additional, Han, Sungyoung, additional, Min, Byoung-Hoon, additional, Jeong, Won Young, additional, Lee, Ga Eul, additional, Kim, Min Sun, additional, Kwon, Seeun, additional, Chung, Hyunwoo, additional, Kang, Hee Jung, additional, and Park, Chung-Gyu, additional

Published
2018
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145. Tacrolimus-induced asymptomatic thrombotic microangiopathy diagnosed by laboratory tests in pig-to-rhesus corneal xenotransplantation: A case report

Author

Kim, Jong-Min, primary, Kim, Jaeyoung, additional, Choi, Se-Hyun, additional, Shin, Jun-Seop, additional, Min, Byoung-Hoon, additional, Jeong, Won Young, additional, Lee, Ga-Eul, additional, Kim, Min-Sun, additional, Kwon, Seeun, additional, Kim, Mee Kum, additional, and Park, Chung-Gyu, additional

Published
2018
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146. In vitro characteristics and in vivo outcome of α1,3-galactosyltransferase gene-knockout miniature pig cornea in full-thickness corneal xenotransplantation using nonhuman primate

Author

Yoon, Chang Ho, primary, Choi, Se Hyun, additional, Lee, Hyun Ju, additional, Kim, Hong Pyo, additional, Kang, Hee Jung, additional, Kim, Jong Min, additional, Choi, Hyuk Jin, additional, Park, Chung-Gyu, additional, Choi, Kimyung, additional, Kim, Hyunil, additional, Ahn, Curie, additional, and Kim, Mee Kum, additional

Published
2018
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