腸管上皮オルガノイドを用いた細胞移植療法の展望
「はじめに」損傷臓器に対する医療として臓器移植が行われるようになって久しいが, 消化管領域における臓器移植医療はfirst lineの治療方法とは言い難い. 移植手術そのものの技術的ハードルが高いことに加え, 適応疾患が短腸症候群, 機能的小腸不全に限られること, ドナー不足や周術期管理の困難さなどから実施件数は伸び悩み, 国内では年間0～3件程度の実施にとどまり, 1995～2015年の間わずか13件である. 臓器移植に代わる再生医療として近年期待されているのが細胞シートやオルガノイドを用いた移植療法である. これは細胞が臓器特異的機能を発揮するために必要な一定の多細胞構造をin vitro...
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| Published in | Japanese Journal of Transplantation Vol. 52; no. 4-5; pp. 332 - 338 |
|---|---|
| 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_332 |
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| Abstract | 「はじめに」損傷臓器に対する医療として臓器移植が行われるようになって久しいが, 消化管領域における臓器移植医療はfirst lineの治療方法とは言い難い. 移植手術そのものの技術的ハードルが高いことに加え, 適応疾患が短腸症候群, 機能的小腸不全に限られること, ドナー不足や周術期管理の困難さなどから実施件数は伸び悩み, 国内では年間0～3件程度の実施にとどまり, 1995～2015年の間わずか13件である. 臓器移植に代わる再生医療として近年期待されているのが細胞シートやオルガノイドを用いた移植療法である. これは細胞が臓器特異的機能を発揮するために必要な一定の多細胞構造をin vitroで再構築し, これを対象部位に移植するものであるが, 体外培養によりレシピエントの細胞を増幅して移植のリソースにできるためドナー不足という問題が生じにくいこと, 再治療等も可能なことなど臓器移植では得られないいくつかの利点があると考えられている. |
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| AbstractList | Organ transplantation is a promising therapy for organ failure and defects of organ specific functions. However, the transplantation of a small or large intestine is difficult to perform partly because of the shortage of donor organs. Alternatively, organoid transplantation is becoming another choice for restoring organ-specific functions. For example, the recent development of 3-D-culture technique for intestinal stem cells has opened up our way to apply those cultured cells to tissue-regenerative therapies. Here we present a short review of studies regarding intestinal organoids established from somatic stem cells or otherwise from pluripotent stem cells. Also, we wish to discuss the possibility of using intestinal organoids as a novel tool for regenerative medicine. 「はじめに」損傷臓器に対する医療として臓器移植が行われるようになって久しいが, 消化管領域における臓器移植医療はfirst lineの治療方法とは言い難い. 移植手術そのものの技術的ハードルが高いことに加え, 適応疾患が短腸症候群, 機能的小腸不全に限られること, ドナー不足や周術期管理の困難さなどから実施件数は伸び悩み, 国内では年間0～3件程度の実施にとどまり, 1995～2015年の間わずか13件である. 臓器移植に代わる再生医療として近年期待されているのが細胞シートやオルガノイドを用いた移植療法である. これは細胞が臓器特異的機能を発揮するために必要な一定の多細胞構造をin vitroで再構築し, これを対象部位に移植するものであるが, 体外培養によりレシピエントの細胞を増幅して移植のリソースにできるためドナー不足という問題が生じにくいこと, 再治療等も可能なことなど臓器移植では得られないいくつかの利点があると考えられている. |
| Author | 岡本, 隆一 渡辺, 守 石橋, 史明 |
| Author_FL | OKAMOTO Ryuichi WATANABE Mamoru ISHIBASHI Fumiaki |
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| References | 19) Spence JR, Mayhew CN, Rankin SA, et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 2011; 470: 105-109. 20) McCracken KW, Howell JC, Wells JM, et al. Generating human intestinal tissue from pluripotent stem cells in vitro. Nat Protoc 2011; 6: 1920-1928. 7) Yui S, Nakamura T, Sato T, et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell. Nat Med 2012; 18: 618-623. 15) Verissimo CS, Overmeer RM, Ponsioen B, et al. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening. Elife 2016; DOI:10.7554/eLife.18489. 2) Mandai M, Watanabe A, Kurimoto Y, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med 2017; 376: 1038-1046. 13) Noben M, Verstockt B, de Bruyn M, et al. Epithelial organoid cultures from patients with ulcerative colitis and Crohn's disease: a truly long-term model to study the molecular basis for inflammatory bowel disease? Gut 2017; DOI:10.1136/gutjnl-2016-313667. 24) Walton KD, Whidden M, Kolterud Å, et al. Villification in the mouse: Bmp signals control intestinal villus patterning. Development 2016; 143: 427-436. 5) Barker N, van Es JH, Kuipers J, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007; 449: 1003-1007. 14) Fujii M, Shimokawa M, Date S, et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 2016; 18: 827-838. 8) van de Wetering M, Francies HE, Francis JM, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 2015; 161: 933-945. 21) Crespo M, Vilar E, Tsai SY, et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nat Med 2017; 23: 878-884. 23) Walker EM, Thompson CA, Battle MA. GATA4 and GATA6 regulate intestinal epithelial cytodifferentiation during development. Dev Biol 2014; 392: 283-294. 3) Abe S, Iyer PG, Oda I, et al. Approaches for stricture prevention after esophageal endoscopic resection. Gastrointest Endosc 2017; 86: 779-791. 10) Sato T, van Es JH, Snippert HJ, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 2011; 469: 415-418. 17) Fukuda M, Mizutani T, Mochizuki W, et al. Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon. Genes Dev 2014; 28: 1752-1757. 18) McCracken KW, Catá EM, Crawford CM, et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 2014; 516: 400-404. 11) Holmberg FE, Seidelin JB, Yin X, et al. Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease. EMBO Mol Med 2017; 9: 558-570. 9) Sato T, Stange DE, Ferrante M, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 2011; 141: 1762-1772. 1) Japan organ transplantation network. https://www.jotnw.or.jp/datafile/offer/year.html 22) Múnera JO, Sundaram N, Rankin SA, et al. Differentiation of human pluripotent stem cells into colonic organoids via transient activation of BMP signaling. Cell Stem Cell 2017; 21: 51-64.e6. 6) Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009; 459: 262-265. 25) Sherwood RI, Maehr R, Mazzoni EO, et al. Wnt signaling specifies and patterns intestinal endoderm. Mech Dev 2011; 128: 387-400. 12) Matano M, Date S, Shimokawa M, et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med 2015; 21: 256-262. 16) Fordham RP, Yui S, Hannan NR, et al. Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury. Cell Stem Cell 2013; 13: 734-744. 4) Potten CS. Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 1977; 269: 518-521. |
| References_xml | – reference: 10) Sato T, van Es JH, Snippert HJ, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 2011; 469: 415-418. – reference: 17) Fukuda M, Mizutani T, Mochizuki W, et al. Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon. Genes Dev 2014; 28: 1752-1757. – reference: 22) Múnera JO, Sundaram N, Rankin SA, et al. Differentiation of human pluripotent stem cells into colonic organoids via transient activation of BMP signaling. Cell Stem Cell 2017; 21: 51-64.e6. – reference: 25) Sherwood RI, Maehr R, Mazzoni EO, et al. Wnt signaling specifies and patterns intestinal endoderm. Mech Dev 2011; 128: 387-400. – reference: 6) Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009; 459: 262-265. – reference: 8) van de Wetering M, Francies HE, Francis JM, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 2015; 161: 933-945. – reference: 15) Verissimo CS, Overmeer RM, Ponsioen B, et al. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening. Elife 2016; DOI:10.7554/eLife.18489. – reference: 3) Abe S, Iyer PG, Oda I, et al. Approaches for stricture prevention after esophageal endoscopic resection. Gastrointest Endosc 2017; 86: 779-791. – reference: 5) Barker N, van Es JH, Kuipers J, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007; 449: 1003-1007. – reference: 2) Mandai M, Watanabe A, Kurimoto Y, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med 2017; 376: 1038-1046. – reference: 7) Yui S, Nakamura T, Sato T, et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell. Nat Med 2012; 18: 618-623. – reference: 11) Holmberg FE, Seidelin JB, Yin X, et al. Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease. EMBO Mol Med 2017; 9: 558-570. – reference: 14) Fujii M, Shimokawa M, Date S, et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 2016; 18: 827-838. – reference: 4) Potten CS. Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 1977; 269: 518-521. – reference: 9) Sato T, Stange DE, Ferrante M, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 2011; 141: 1762-1772. – reference: 20) McCracken KW, Howell JC, Wells JM, et al. Generating human intestinal tissue from pluripotent stem cells in vitro. Nat Protoc 2011; 6: 1920-1928. – reference: 24) Walton KD, Whidden M, Kolterud Å, et al. Villification in the mouse: Bmp signals control intestinal villus patterning. Development 2016; 143: 427-436. – reference: 1) Japan organ transplantation network. https://www.jotnw.or.jp/datafile/offer/year.html – reference: 12) Matano M, Date S, Shimokawa M, et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med 2015; 21: 256-262. – reference: 13) Noben M, Verstockt B, de Bruyn M, et al. Epithelial organoid cultures from patients with ulcerative colitis and Crohn's disease: a truly long-term model to study the molecular basis for inflammatory bowel disease? Gut 2017; DOI:10.1136/gutjnl-2016-313667. – reference: 18) McCracken KW, Catá EM, Crawford CM, et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 2014; 516: 400-404. – reference: 19) Spence JR, Mayhew CN, Rankin SA, et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 2011; 470: 105-109. – reference: 16) Fordham RP, Yui S, Hannan NR, et al. Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury. Cell Stem Cell 2013; 13: 734-744. – reference: 21) Crespo M, Vilar E, Tsai SY, et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nat Med 2017; 23: 878-884. – reference: 23) Walker EM, Thompson CA, Battle MA. GATA4 and GATA6 regulate intestinal epithelial cytodifferentiation during development. Dev Biol 2014; 392: 283-294. |
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| Snippet | 「はじめに」損傷臓器に対する医療として臓器移植が行われるようになって久しいが, 消化管領域における臓器移植医療はfirst lineの治療方法とは言い難い. 移植手... Organ transplantation is a promising therapy for organ failure and defects of organ specific functions. However, the transplantation of a small or large... |
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| SubjectTerms | induced pluripotent stem cell inflammatory bowel disease intestinal organoid transplantation |
| Title | 腸管上皮オルガノイドを用いた細胞移植療法の展望 |
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