異種移植の現況
臓器移植を歴史的に振り返ると,動物からヒトへの異種移植が,ヒトからヒトへの同種移植に先行して,1900年代には既に試みられている.脳死の定義ができるまでは同種移植は心停止ドナーあるいは生体ドナー以外になかったので,1960年代に主にconcordant系の動物である霊長類からヒトへの異種移植が実施されたが成功例はなかった.脳死移植が進み,一時期異種移植は臨床で行われなくなったが,異種移植における拒絶反応の機序が明らかとなったことと,発生工学手法の核移植が可能となったことから,異種移植用のブタの開発がブームとなった.しかし,当時は複数の遺伝子改変ができなかったため,ブームは数年で終わった.その後...
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Published in | Organ Biology Vol. 30; no. 1; pp. 015 - 027 |
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Main Author | |
Format | Journal Article |
Language | Japanese |
Published |
一般社団法人 日本臓器保存生物医学会
2023
日本臓器保存生物医学会 |
Subjects | |
Online Access | Get full text |
ISSN | 1340-5152 2188-0204 |
DOI | 10.11378/organbio.30.015 |
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Abstract | 臓器移植を歴史的に振り返ると,動物からヒトへの異種移植が,ヒトからヒトへの同種移植に先行して,1900年代には既に試みられている.脳死の定義ができるまでは同種移植は心停止ドナーあるいは生体ドナー以外になかったので,1960年代に主にconcordant系の動物である霊長類からヒトへの異種移植が実施されたが成功例はなかった.脳死移植が進み,一時期異種移植は臨床で行われなくなったが,異種移植における拒絶反応の機序が明らかとなったことと,発生工学手法の核移植が可能となったことから,異種移植用のブタの開発がブームとなった.しかし,当時は複数の遺伝子改変ができなかったため,ブームは数年で終わった.その後,複数遺伝子の改変法が開発され,ブタから霊長類への同所性心臓移植の長期生存例が報告されるようになり,2022年1月ブタからヒトへの遺伝子改変ブタの心臓移植が実施された.ここでは,異種移植の歴史を振り返りながら,筆者の霊長類を用いた異種移植の研究経験を紹介しながら,今回の事例について考察する. |
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AbstractList | 臓器移植を歴史的に振り返ると,動物からヒトへの異種移植が,ヒトからヒトへの同種移植に先行して,1900年代には既に試みられている.脳死の定義ができるまでは同種移植は心停止ドナーあるいは生体ドナー以外になかったので,1960年代に主にconcordant系の動物である霊長類からヒトへの異種移植が実施されたが成功例はなかった.脳死移植が進み,一時期異種移植は臨床で行われなくなったが,異種移植における拒絶反応の機序が明らかとなったことと,発生工学手法の核移植が可能となったことから,異種移植用のブタの開発がブームとなった.しかし,当時は複数の遺伝子改変ができなかったため,ブームは数年で終わった.その後,複数遺伝子の改変法が開発され,ブタから霊長類への同所性心臓移植の長期生存例が報告されるようになり,2022年1月ブタからヒトへの遺伝子改変ブタの心臓移植が実施された.ここでは,異種移植の歴史を振り返りながら,筆者の霊長類を用いた異種移植の研究経験を紹介しながら,今回の事例について考察する. 「要旨」臓器移植を歴史的に振り返ると, 動物からヒトへの異種移植が, ヒトからヒトへの同種移植に先行して, 1900年代には既に試みられている. 脳死の定義ができるまでは同種移植は心停止ドナーあるいは生体ドナー以外になかったので, 1960年代に主にconcordant系の動物である霊長類からヒトへの異種移植が実施されたが成功例はなかった. 脳死移植が進み, 一時期異種移植は臨床で行われなくなったが, 異種移植における拒絶反応の機序が明らかとなったことと, 発生工学手法の核移植が可能となったことから, 異種移植用のブタの開発がブームとなった. しかし, 当時は複数の遺伝子改変ができなかったため, ブームは数年で終わった. その後, 複数遺伝子の改変法が開発され, ブタから霊長類への同所性心臓移植の長期生存例が報告されるようになり, 2022年1月ブタからヒトへの遺伝子改変ブタの心臓移植が実施された. ここでは, 異種移植の歴史を振り返りながら, 筆者の霊長類を用いた異種移植の研究経験を紹介しながら, 今回の事例について考察する. |
Author | 福嶌, 教偉 |
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References | 26) Fukushima N, Gundry SR, Matsumiya G, Bouchart F, Zuppan C, Bailey LL. Histological findings in heart grafts after orthotopic pig to baboon cardiac transplantation. Transplant Proc 1996;28:788-790 31) Cleveland DC, Jagdale A, Carlo WF, et al. The Genetically Engineered Heart as a Bridge to Allotransplantation in Infants Just Around the Corner? Ann Thorac Surg 2022;114(2):536-544 1) Jaboulay, M, Greffe du Reins au pli du Coude par Soudures Arterielles et Veineuses. Lyon Med 1906;107:575-577 4) Neuhof H. The Transplantation of Tissues. Appleton, New York, 1923 5) Reemtsma K, McCracken BH, Schegel JU, et al. Renal Hetero transplantation in Man. Ann Surg 1964;160:384 13) Barnard CN. The operation. A human cardiac transplant: An interim report of a successful operation performed at Groote Schuur hospital, Cape Town. S Afr Med J 1967;41:1271-1274 27) Miyagawa S, Murakami H, Takahagi Y, et al. Remodeling of the major pig xenoantigen by N-acetylglucosaminyltransferase III in transgenic pig. J Biol Chem 2001;276(42):39310-39319 18) Kawauchi M, Gundry SR, Alonso de Bogona J, Beierle F, Bailey LL. Plasma level of FK 506 in newborn goats and infant baboons. Transplant Proc 1991;23:2755-2756 10) Hardy JD, Chavez CM, Kurrus FD, et al. Heart transplantation in human. JAMA 1964;188:1132-1140. 11) Starzl TE, Marchioro TL, Faris TD, McCardle RJ, Iwaski Y. Avenues of future research in homotransplantation of the liver with particular reference to hepatic supportive procedures, antilymphocyte serum, and tissue typing. Am J Surg 1966;112:391-400 21) Kawauchi M, Gundry SR, Alonso de Begona J, Razzouk AJ, et al. Prolonged survival of orthotopically transplanted heart xenograft in infant baboons. The Journal of Thoracic and Cardiovascular Surgery. 1993;106:779-786 23) Fukushima N, Kawauchi M, Bouchart F, Gundry SR, Zuppan CW, Ruiz CE, et al. Graft atherosclerosis in concordant cardiac transplantation. Transplant Proc 1994;26:1059-1060 17) Griffith BP, Goerlich CE, Singh AK, et al. Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. N Engl J Med 2022;387(1):35-44. 28) Fujita T, Miyagawa S, Ezoe K, et al. Skin graft of double transgenic pigs of N-acetylglucosaminyltransferase III (GnT-III) and DAF (CD55) genes survived in cynomolgus monkey for 31 days. Transpl Immunol 2004;13(4):259-264 25) Fukushima N, Bouchart F, Gundry SR, Nehlsen-Cannarella S, Gusewitch G, Chang L, et al. The role of anti-pig antibody in pig-to-baboon cardiac xenotransplant rejection. Transplantation 1994;57:923-928 30) Längin M, Mayr T, Reichart B, et al. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature 2018;564(7736):430-433. 19) Alonso de Begona J, Gundry S, Kawauchi M, Bailey LL, et al. Assessment of baboon lymphocyte subsets and activity in cardiac xenobridging to allotransplantation. Transplant Proc 1992;24:453-454 32) Hinrichs A, Riedel EO, Klymiuk N, et al. Growth hormone receptor knockout to reduce the size of donor pigs for preclinical xenotransplantation studies. Xenotransplantation 2021;28:e12664. 6) Voronoy U. Sobre Bloqueo del Aparato Reticuloen-dotelil del Hombre an Algunas Formas de Intoxicacion por el Sublimado y Sobre la Transplantacion del Rinon Cadaverico. Siglo Medico 1937;97:296-297 9) Starzl TE, Marchioro TL, Pteres GN, Kirkpatrick CH. Renal Heterotransplantation from Baboon to Man: Experience with 6 cases. Transplantation 1964;2:752 16) Starzl TE, Fung J, Tzakis A, et al Baboon-to-Human Liver Transplantation. Lancet 1993;341:65-71 2) Princeteau M. Greffe rénale. J Méd Bordeaux. 1905;26:549. 8) Hitchcock CR, Kiser JC, Telander RL, Seljeskog EL. Baboon renal grafts. JAMA 1964;189:158-161. 12) Barnard CN, Wolpowitz A, Losman JG. Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass. S Afr Med J 1977;52:1035-1039 3) Unger, E. Nierentransplantation. Wein Klin Wochenschr 1910;47:573-578 29) Mohiuddin MM, Singh AK, Corcoran PC, et al. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft Nat Commun 2016;7:11138. 24) Fukushima N, Fagoaga O, Bouchart F, Grinde S, Gusewitch G, Thorpe R, et al. Comparison of newborn versus adult natural heterophile anti-pig red blood cell IgM xenoantibodies as correlates of xenograft survival. Transplant Proc 1994;26:1395-1396 20) Michler RE, O’Hair DP, Xu H, Shah AS, Itescu S. Newborn baboon immunity: Lessons in cross-species transplantation. Ann Thorac Surg 1995;60:S581 14) Bailey LL, Nehlsen-Cannarella S, Concepcion W, et al. Baboon-to-human cardiac xenotransplantation in a neonate. J Am Med Assoc 1985:254;3321-3329 7) Murray, JE, Merrill, JP, Harrison, JH Renal Homotransp-lanta tion in Identical Twins. Surg Forum, 1955;6:432 22) Fukushima N, Fagoaga O, Kawauchi M, et al. Lymphocyte subset markers as predictors of survival after concordant cardiac xenotransplantation. Transplant Proc 1994;26:1212-1213 15) Makowka L, Wu GD, Hoffman A, et al. Immunohistopathologic lesions associated with the rejection of a pig-to-human liver xenograft. Transplant Proc 1994;26:1074-1075. |
References_xml | – reference: 26) Fukushima N, Gundry SR, Matsumiya G, Bouchart F, Zuppan C, Bailey LL. Histological findings in heart grafts after orthotopic pig to baboon cardiac transplantation. Transplant Proc 1996;28:788-790 – reference: 31) Cleveland DC, Jagdale A, Carlo WF, et al. The Genetically Engineered Heart as a Bridge to Allotransplantation in Infants Just Around the Corner? Ann Thorac Surg 2022;114(2):536-544 – reference: 1) Jaboulay, M, Greffe du Reins au pli du Coude par Soudures Arterielles et Veineuses. Lyon Med 1906;107:575-577 – reference: 24) Fukushima N, Fagoaga O, Bouchart F, Grinde S, Gusewitch G, Thorpe R, et al. Comparison of newborn versus adult natural heterophile anti-pig red blood cell IgM xenoantibodies as correlates of xenograft survival. Transplant Proc 1994;26:1395-1396 – reference: 18) Kawauchi M, Gundry SR, Alonso de Bogona J, Beierle F, Bailey LL. Plasma level of FK 506 in newborn goats and infant baboons. Transplant Proc 1991;23:2755-2756 – reference: 21) Kawauchi M, Gundry SR, Alonso de Begona J, Razzouk AJ, et al. Prolonged survival of orthotopically transplanted heart xenograft in infant baboons. The Journal of Thoracic and Cardiovascular Surgery. 1993;106:779-786 – reference: 27) Miyagawa S, Murakami H, Takahagi Y, et al. Remodeling of the major pig xenoantigen by N-acetylglucosaminyltransferase III in transgenic pig. J Biol Chem 2001;276(42):39310-39319 – reference: 7) Murray, JE, Merrill, JP, Harrison, JH Renal Homotransp-lanta tion in Identical Twins. Surg Forum, 1955;6:432 – reference: 23) Fukushima N, Kawauchi M, Bouchart F, Gundry SR, Zuppan CW, Ruiz CE, et al. Graft atherosclerosis in concordant cardiac transplantation. Transplant Proc 1994;26:1059-1060 – reference: 5) Reemtsma K, McCracken BH, Schegel JU, et al. Renal Hetero transplantation in Man. Ann Surg 1964;160:384 – reference: 11) Starzl TE, Marchioro TL, Faris TD, McCardle RJ, Iwaski Y. Avenues of future research in homotransplantation of the liver with particular reference to hepatic supportive procedures, antilymphocyte serum, and tissue typing. Am J Surg 1966;112:391-400 – reference: 16) Starzl TE, Fung J, Tzakis A, et al Baboon-to-Human Liver Transplantation. Lancet 1993;341:65-71 – reference: 9) Starzl TE, Marchioro TL, Pteres GN, Kirkpatrick CH. Renal Heterotransplantation from Baboon to Man: Experience with 6 cases. Transplantation 1964;2:752 – reference: 8) Hitchcock CR, Kiser JC, Telander RL, Seljeskog EL. Baboon renal grafts. JAMA 1964;189:158-161. – reference: 14) Bailey LL, Nehlsen-Cannarella S, Concepcion W, et al. Baboon-to-human cardiac xenotransplantation in a neonate. J Am Med Assoc 1985:254;3321-3329 – reference: 28) Fujita T, Miyagawa S, Ezoe K, et al. Skin graft of double transgenic pigs of N-acetylglucosaminyltransferase III (GnT-III) and DAF (CD55) genes survived in cynomolgus monkey for 31 days. Transpl Immunol 2004;13(4):259-264 – reference: 13) Barnard CN. The operation. A human cardiac transplant: An interim report of a successful operation performed at Groote Schuur hospital, Cape Town. S Afr Med J 1967;41:1271-1274 – reference: 25) Fukushima N, Bouchart F, Gundry SR, Nehlsen-Cannarella S, Gusewitch G, Chang L, et al. The role of anti-pig antibody in pig-to-baboon cardiac xenotransplant rejection. Transplantation 1994;57:923-928 – reference: 29) Mohiuddin MM, Singh AK, Corcoran PC, et al. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft Nat Commun 2016;7:11138. – reference: 12) Barnard CN, Wolpowitz A, Losman JG. Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass. S Afr Med J 1977;52:1035-1039 – reference: 19) Alonso de Begona J, Gundry S, Kawauchi M, Bailey LL, et al. Assessment of baboon lymphocyte subsets and activity in cardiac xenobridging to allotransplantation. Transplant Proc 1992;24:453-454 – reference: 4) Neuhof H. The Transplantation of Tissues. Appleton, New York, 1923 – reference: 10) Hardy JD, Chavez CM, Kurrus FD, et al. Heart transplantation in human. JAMA 1964;188:1132-1140. – reference: 22) Fukushima N, Fagoaga O, Kawauchi M, et al. Lymphocyte subset markers as predictors of survival after concordant cardiac xenotransplantation. Transplant Proc 1994;26:1212-1213 – reference: 15) Makowka L, Wu GD, Hoffman A, et al. Immunohistopathologic lesions associated with the rejection of a pig-to-human liver xenograft. Transplant Proc 1994;26:1074-1075. – reference: 20) Michler RE, O’Hair DP, Xu H, Shah AS, Itescu S. Newborn baboon immunity: Lessons in cross-species transplantation. Ann Thorac Surg 1995;60:S581 – reference: 32) Hinrichs A, Riedel EO, Klymiuk N, et al. Growth hormone receptor knockout to reduce the size of donor pigs for preclinical xenotransplantation studies. Xenotransplantation 2021;28:e12664. – reference: 3) Unger, E. Nierentransplantation. Wein Klin Wochenschr 1910;47:573-578 – reference: 17) Griffith BP, Goerlich CE, Singh AK, et al. Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. N Engl J Med 2022;387(1):35-44. – reference: 6) Voronoy U. Sobre Bloqueo del Aparato Reticuloen-dotelil del Hombre an Algunas Formas de Intoxicacion por el Sublimado y Sobre la Transplantacion del Rinon Cadaverico. Siglo Medico 1937;97:296-297 – reference: 30) Längin M, Mayr T, Reichart B, et al. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature 2018;564(7736):430-433. – reference: 2) Princeteau M. Greffe rénale. J Méd Bordeaux. 1905;26:549. |
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Snippet | ... 「要旨」臓器移植を歴史的に振り返ると, 動物からヒトへの異種移植が, ヒトからヒトへの同種移植に先行して, 1900年代には既に試みられている. 脳死の定義ができるまでは同種移植は心停止ドナーあるいは生体ドナー以外になかったので,... |
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SubjectTerms | concordant系 discordant系 抗体関連型拒絶 異種移植 遺伝子改変 |
Title | 異種移植の現況 |
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