臓器置換を目指す肝オルガノイド研究の新展開
「はじめに」臨床的有効性が明確である移植医療において, その最重要課題がドナー臓器の絶対的不足への対応であることは明らかである. 例えば, 米国における臓器移植の実施件数と待機人数との乖離は, 1989年には数千名の範囲内に収まっていたにもかかわらず, その後の乖離状況は悪化の一途をたどっており, 2013年には10万人近くに著明に増大しているのが現状である (United Network for Organ Sharing : UNOS). すなわち, 米国だけで, 毎年, なんと10万人近くの臓器不全患者が移植手術を待ちながら移植を受けることができない状況が厳然として存在しているのである....
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| Published in | Japanese Journal of Transplantation Vol. 52; no. 4-5; pp. 310 - 317 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本移植学会
2017
日本移植学会 The Japan Society for Transplantation |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0578-7947 2188-0034 |
| DOI | 10.11386/jst.52.4-5_310 |
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| Abstract | 「はじめに」臨床的有効性が明確である移植医療において, その最重要課題がドナー臓器の絶対的不足への対応であることは明らかである. 例えば, 米国における臓器移植の実施件数と待機人数との乖離は, 1989年には数千名の範囲内に収まっていたにもかかわらず, その後の乖離状況は悪化の一途をたどっており, 2013年には10万人近くに著明に増大しているのが現状である (United Network for Organ Sharing : UNOS). すなわち, 米国だけで, 毎年, なんと10万人近くの臓器不全患者が移植手術を待ちながら移植を受けることができない状況が厳然として存在しているのである. 致死的な重症肝不全患者を対象とする肝臓移植においては, 米国における1年間に新規発生する待機リスト登録者約17,000名のうち, 実に約4,000名の患者が臓器移植を待ちながら, ドナー肝臓が届くことなく死亡している. |
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| AbstractList | The self-organizing tissue-based approach coupled with induced pluripotent stem (iPS) cell technology is evolving as a promising field for designing organoids in culture; it is expected to achieve valuable practical outcomes in regenerative medicine and drug development. Organoids show properties of functional organs and represent an alternative to cell models in conventional two-dimensional differentiation platforms; moreover, organoids can be used to investigate mechanisms of development and disease, drug discovery and toxicity assessment. Here we review characters of emerging organoid technology focusing on liver bud as an example, and discuss their promise and challenges for the use regenerative medicine. 「はじめに」臨床的有効性が明確である移植医療において, その最重要課題がドナー臓器の絶対的不足への対応であることは明らかである. 例えば, 米国における臓器移植の実施件数と待機人数との乖離は, 1989年には数千名の範囲内に収まっていたにもかかわらず, その後の乖離状況は悪化の一途をたどっており, 2013年には10万人近くに著明に増大しているのが現状である (United Network for Organ Sharing : UNOS). すなわち, 米国だけで, 毎年, なんと10万人近くの臓器不全患者が移植手術を待ちながら移植を受けることができない状況が厳然として存在しているのである. 致死的な重症肝不全患者を対象とする肝臓移植においては, 米国における1年間に新規発生する待機リスト登録者約17,000名のうち, 実に約4,000名の患者が臓器移植を待ちながら, ドナー肝臓が届くことなく死亡している. |
| Author | 武部, 貴則 谷口, 英樹 |
| Author_FL | 武部 貴則 TANIGUCHI Hideki |
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| Copyright | 2017 一般社団法人 日本移植学会 |
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| References_xml | – reference: 16) Zemel A, Rehfeldt F, Brown AE, et al. Optimal matrix rigidity for stress fiber polarization in stem cells. Nat Phys 2010; 6: 468-473. – reference: 22) Ståhl PL, Salmén F, Vickovic S, et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 2016; 353: 78-82. – reference: 9) Zorn AM. Liver development. https://www.ncbi.nlm.nih.gov/books/NBK27068/ – reference: 26) Cahan P, Li H, Morris SA, et al. CellNet: network biology applied to stem cell engineering. Cell 2014; 158: 903-915. – reference: 15) Engler AJ, Sen S, Sweeney HL, et al. Matrix elasticity directs stem cell lineage specification. Cell 2006; 126: 677-689. – reference: 10) Matsumoto K, Yoshitomi H, Rossant J, et al. Liver organogenesis promoted by endothelial cells prior to vascular function. Science 2001; 294: 559-563. – reference: 20) Hyun I, Wilkerson A, Johnston J. Embryology policy: revisit the 14-day rule. Nature 2016; 533: 169-171. – reference: 19) Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 2004; 3: 711-715. – reference: 14) Wolf K, Mazo I, Leung H, et al. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 2003; 160: 267-277. – reference: 25) Roost MS, van Iperen L, Ariyurek Y, et al. KeyGenes, a tool to probe tissue differentiation using a human fetal transcriptional atlas. Stem Cell Reports 2015; 4: 1112-1124. – reference: 12) Takebe T, Enomura M, Yoshizawa E, et al. Vascularized and complex organ buds from diverse tissues via mesenchymal cell-driven condensation. Cell Stem Cell 2015; 16: 556-565. – reference: 21) Camp JG, Badsha F, Florio M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci USA 2015; 112: 15672-15677. – reference: 17) Sasai Y. Cytosystems dynamics in self-organization of tissue architecture. Nature 2013; 493: 318-326. – reference: 3) Duncan AW, Dorrell C, Grompe M. Stem cells and liver regeneration. Gastroenterology 2009; 137: 466-481. – reference: 5) Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 2013; 494: 247-250. – reference: 11) Takebe T, Sekine K, Enomura M, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013; 499: 481-484. – reference: 1) Rashid ST, Corbineau S, Hannan N, et al. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest 2010; 120: 3127-3136. – reference: 24) Buettner F, Natarajan KN, Casale FP, et al. Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells. Nat Biotechnol 2015; 33: 155-160. – reference: 4) Wang B, Zhao L, Fish M, et al. Self-renewing diploid Axin2（+） cells fuel homeostatic renewal of the liver. Nature 2015; 524: 180-185. – reference: 6) Huch M, Gehart H, Van Boxtel R, et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 2015; 160: 299-312. – reference: 2) Llovet JM, Mas X, Aponte JJ, et al. Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation. Gut 2002; 50: 123-128. – reference: 18) Ingber DE. Reverse engineering human pathophysiology with organs-on-chips. Cell 2016; 164: 1105-1109. – reference: 8) Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev Cell 2010; 18: 175-189. – reference: 7) Si-Tayeb K, Noto FK, Nagaoka M, et al. Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 2010; 51: 297-305. – reference: 23) Nichterwitz S, Chen G, Aguila Benitez J, et al. Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling. Nat Commun 2016; 7: 12139. – reference: 13) Dourdin N, Bhatt AK, Dutt P, et al. Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts. J Biol Chem 2001; 276: 48382-48388. |
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| Snippet | 「はじめに」臨床的有効性が明確である移植医療において, その最重要課題がドナー臓器の絶対的不足への対応であることは明らかである. 例えば, 米国における臓器移植の実施件数と待機人数との乖離は, 1989年には数千名の範囲内に収まっていたにもかかわらず, その後の乖離状況は悪化の一途をたどっており,... The self-organizing tissue-based approach coupled with induced pluripotent stem (iPS) cell technology is evolving as a promising field for designing organoids... |
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| SubjectTerms | iPS cell liver bud mini-organ organoid regenerative medicine self-condensation self-organization transplantation |
| Title | 臓器置換を目指す肝オルガノイド研究の新展開 |
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