多能性幹細胞を用いた 膵 β 細胞分化誘導研究の最新動向

膵β細胞は, 唯一の血糖降下作用ホルモンであるインスリンを分泌する細胞である. この膵β細胞が喪失し, インスリンが枯渇する糖尿病患者に対する根治療法として膵・膵島移植が行われている. しかしながら, 膵・膵島移植はドナー数不足という問題を抱えており, これを解決しうる方法の一つとして再生医療が期待されている. 一般に, 膵β細胞はin vitroで増殖させることが困難である. そこで, 代替細胞を供給する方法として自己複製能と多分化能を有する幹細胞を用いた機能的な膵β細胞の分化誘導法の開発が世界中で試みられている. 数ある幹細胞のなかでも多能性を有している二つの細胞, すなわち, 受精卵の胚...

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Published inOrgan Biology Vol. 21; no. 2; pp. 228 - 236
Main Authors 髙橋, 禎暢, 武部, 貴則, 谷口, 英樹
Format Journal Article
LanguageJapanese
Published 一般社団法人 日本臓器保存生物医学会 10.07.2014
日本臓器保存生物医学会
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ISSN1340-5152
2188-0204
DOI10.11378/organbio.21.228

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Abstract 膵β細胞は, 唯一の血糖降下作用ホルモンであるインスリンを分泌する細胞である. この膵β細胞が喪失し, インスリンが枯渇する糖尿病患者に対する根治療法として膵・膵島移植が行われている. しかしながら, 膵・膵島移植はドナー数不足という問題を抱えており, これを解決しうる方法の一つとして再生医療が期待されている. 一般に, 膵β細胞はin vitroで増殖させることが困難である. そこで, 代替細胞を供給する方法として自己複製能と多分化能を有する幹細胞を用いた機能的な膵β細胞の分化誘導法の開発が世界中で試みられている. 数ある幹細胞のなかでも多能性を有している二つの細胞, すなわち, 受精卵の胚からつくる胚性幹細胞(embryonic stem cells, ES細胞)と, ヒトの皮膚などの細胞をリプログラミングし作製する人工多能性幹細胞(induced pluripotent stem cells, iPS細胞)を用いた手法に注目が集まっている.
AbstractList 膵β細胞は, 唯一の血糖降下作用ホルモンであるインスリンを分泌する細胞である. この膵β細胞が喪失し, インスリンが枯渇する糖尿病患者に対する根治療法として膵・膵島移植が行われている. しかしながら, 膵・膵島移植はドナー数不足という問題を抱えており, これを解決しうる方法の一つとして再生医療が期待されている. 一般に, 膵β細胞はin vitroで増殖させることが困難である. そこで, 代替細胞を供給する方法として自己複製能と多分化能を有する幹細胞を用いた機能的な膵β細胞の分化誘導法の開発が世界中で試みられている. 数ある幹細胞のなかでも多能性を有している二つの細胞, すなわち, 受精卵の胚からつくる胚性幹細胞(embryonic stem cells, ES細胞)と, ヒトの皮膚などの細胞をリプログラミングし作製する人工多能性幹細胞(induced pluripotent stem cells, iPS細胞)を用いた手法に注目が集まっている.
Author 髙橋, 禎暢
武部, 貴則
谷口, 英樹
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4) Miyazaki S, Yamato E, Miyazaki J. Regulated expression of pdx-1 promotes in vitro differentiation of insulin producing cells from embryonic stem cells. Diabetes 53 (4): 1030-1037, 2004
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1) Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R,McKay R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292(5520): 1389-1394, 2001. Epub 2001 Apr 26
7) Gradwohl G, Dierich A, LeMeur M, Guillemot F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci USA 97(4): 1607-1611, 2000
2) Afrikanova I, Yebra M, Simpkinson M, Xu Y, Hayek A,Montgomery A. Inhibitors of Src and focal adhesion kinase promote endocrine specification: impact on the derivation of b-cells from human pluripotent stem cells. J Biol Chem 286(41): 36042-36052, 2011. doi: 10.1074 /jbc.M111.290825. Epub 2011 Aug 18
13) Alipio Z, Liao W, Roemer EJ, Waner M, Fink LM, Ward DC, Ma Y. Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells. Proc Natl Acad Sci USA 107 (30): 13426-13431, 2010. doi: 10.1073/pnas.1007884107 Epub 2010 Jul 7
22) Tateishi K, He J, Taranova O, Liang G, DʼAlessio AC,Zhang Y. Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem 283 (46): 31601-31607, 2008. doi: 10.1074/jbc.M806597200 Epub 2008 Sep 9
24) Hua H, Shang L, Martinez H, Freeby M, Gallagher MP,Ludwig T, Deng L, Greenberg E, Leduc C, Chung WK, Goland R, Leibel RL, Egli D. iPSC-derived b cells model diabetes due to glucokinase deficiency. J Clin Invest 123 (7): 3146-3153, 2013. doi: 10.1172/JCI67638 Epub 2013 Jun 17
31) Wang RN, Klöppel G, Bouwens L. Duct- to islet-cell differentiation and islet growth in the pancreas of ductligated adult rats. Diabetologia 38(12): 1405-1411, 1995
21) Maehr R, Chen S, Snitow M, Ludwig T, Yagasaki L, Goland R, Leibel RL, Melton DA. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci USA 106(37): 15768-15773, 2009. doi: 10.1073/pnas. 0906894106 Epub 2009 Aug 31
9) Yasunaga M, Tada S, Torikai-Nishikawa S, Nakano Y, Okada M, Jakt LM, Nishikawa S, Chiba T, Era T, Nishikawa S. Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 23(12): 1542-1550, 2005. Epub 2005 Nov 27
16) Ohmine S, Squillace KA, Hartjes KA, Deeds MC, Armstrong AS, Thatava T, Sakuma T, Terzic A, Kudva Y,Ikeda Y. Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency. Aging(Albany NY) 4(1): 60-73,2012
20) Chen S, Borowiak M, Fox JL, Maehr R, Osafune K, Davidow L, Lam K, Peng LF, Schreiber SL, Rubin LL,Melton D. A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol 5 (4): 258-265, 2009. doi: 10.1038/nchembio. 154 Epub 2009 Mar 15
11) Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG,Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, DʼAmour KA, Carpenter MK, Baetge EE. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26 (4): 443-452, 2008. doi:10.1038/nbt1393 Epub 2008 Feb 20
23) Zhang D, Jiang W, Liu M, Sui X, Yin X, Chen S, Shi Y,Deng H. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res 19(4): 429-438, 2009. doi: 10.1038/cr. 2009.28
25) Thatava T, Kudva YC, Edukulla R, Squillace K, De Lamo JG, Khan YK, Sakuma T, Ohmine S, Terzic A, Ikeda Y. Intrapatient variations in type 1 diabetes-specific iPS cell differentiation into insulin-producing cells. Mol Ther 21 (1): 228-239, 2013. doi: 10.1038/mt. 2012.245 Epub 2012 Nov 27
34) Rankin MM, Wilbur CJ, Rak K, Shields EJ, Granger A, Kushner JA. b-Cells are not generated in pancreatic duct ligation-induced injury in adult mice. Diabetes 62(5):1634-1645, 2013. doi: 10.2337/db12-0848 Epub 2013 Jan 24
17) Thatava T, Nelson TJ, Edukulla R, Sakuma T, Ohmine S, Tonne JM, Yamada S, Kudva Y, Terzic A, Ikeda Y. Indolactam V/GLP-1-mediated differentiation of human iPS cells into glucose-responsive insulin-secreting progeny. Gene Ther 18(3): 283-293, 2011. doi: 10.1038/gt. 2010.145 Epub 2010 Nov 4
References_xml – reference: 23) Zhang D, Jiang W, Liu M, Sui X, Yin X, Chen S, Shi Y,Deng H. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res 19(4): 429-438, 2009. doi: 10.1038/cr. 2009.28
– reference: 18) Zhang D, Jiang W, Liu M, Sui X, Yin X, Chen S, Shi Y,Deng H. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res 19(4): 429-438, 2009. doi: 10.1038/cr. 2009.28
– reference: 15) Kunisada Y, Tsubooka-Yamazoe N, Shoji M, Hosoya M. Small molecules induce efficient differentiation into insulin-producing cells from human induced pluripotent stem cells. Stem Cell Res 8 (2): 274-284, 2012. doi:10.1016/j.scr.2011.10.002 Epub 2011 Oct 11
– reference: 33) Chintinne M, Stangé G, Denys B, Ling Z, Inʼt Veld P, Pipeleers D. Beta cell count instead of beta cell mass to assess and localize growth in beta cell population following pancreatic duct ligation in mice. PLoS One 7(8): e43959,2012. doi: 10.1371/journal.pone.0043959 Epub 2012 Aug 30
– reference: 19) Jiang J, Au M, Lu K, Eshpeter A, Korbutt G, Fisk G, Majumdar AS. Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25 (8): 1940-1953, 2007. Epub 2007 May 17
– reference: 31) Wang RN, Klöppel G, Bouwens L. Duct- to islet-cell differentiation and islet growth in the pancreas of ductligated adult rats. Diabetologia 38(12): 1405-1411, 1995
– reference: 36) Saito H, Takeuchi M, Chida K, Miyajima A. Generation of glucose-responsive functional islets with a three-dimen sional structure from mouse fetal pancreatic cells and iPS cells in vitro. PLoS One 6(12): e28209, 2011. doi: 10. 1371/journal.pone.0028209 Epub 2011 Dec 1
– reference: 13) Alipio Z, Liao W, Roemer EJ, Waner M, Fink LM, Ward DC, Ma Y. Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells. Proc Natl Acad Sci USA 107 (30): 13426-13431, 2010. doi: 10.1073/pnas.1007884107 Epub 2010 Jul 7
– reference: 16) Ohmine S, Squillace KA, Hartjes KA, Deeds MC, Armstrong AS, Thatava T, Sakuma T, Terzic A, Kudva Y,Ikeda Y. Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency. Aging(Albany NY) 4(1): 60-73,2012
– reference: 1) Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R,McKay R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292(5520): 1389-1394, 2001. Epub 2001 Apr 26
– reference: 6) Bernardo AS, Cho CH, Mason S, Docherty HM, Pedersen RA, Vallier L, Docherty K. Biphasic induction of Pdx1 in mouse and human embryonic stem cells can mimic development of pancreatic beta-cells. Stem Cells 27(2):341-351, 2009. doi: 10.1634/stemcells.2008-0310
– reference: 17) Thatava T, Nelson TJ, Edukulla R, Sakuma T, Ohmine S, Tonne JM, Yamada S, Kudva Y, Terzic A, Ikeda Y. Indolactam V/GLP-1-mediated differentiation of human iPS cells into glucose-responsive insulin-secreting progeny. Gene Ther 18(3): 283-293, 2011. doi: 10.1038/gt. 2010.145 Epub 2010 Nov 4
– reference: 32) Xu X, DʼHoker J, Stangé G, Bonné S, De Leu N, Xiao X, Van de Casteele M, Mellitzer G, Ling Z, Pipeleers D,Bouwens L, Scharfmann R, Gradwohl G, Heimberg H. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132 (2): 197-207,2008. doi: 10.1016/j.cell.2007.12.015
– reference: 2) Afrikanova I, Yebra M, Simpkinson M, Xu Y, Hayek A,Montgomery A. Inhibitors of Src and focal adhesion kinase promote endocrine specification: impact on the derivation of b-cells from human pluripotent stem cells. J Biol Chem 286(41): 36042-36052, 2011. doi: 10.1074 /jbc.M111.290825. Epub 2011 Aug 18
– reference: 26) Nostro MC, Sarangi F, Ogawa S, Holtzinger A, Corneo B, Li X, Micallef SJ, Park IH, Basford C, Wheeler MB, Daley GQ, Elefanty AG, Stanley EG, Keller G. Stage-specific signaling through TGFb family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells. Development 138 (5): 861-871,2011. doi: 10.1242/dev.055236 Epub 2011 Jan 26
– reference: 4) Miyazaki S, Yamato E, Miyazaki J. Regulated expression of pdx-1 promotes in vitro differentiation of insulin producing cells from embryonic stem cells. Diabetes 53 (4): 1030-1037, 2004
– reference: 29) Zhou Q, Melton DA. Extreme makeover: converting one cell into another. Cell Stem Cell 3(4): 382-388, 2008. doi: 10.1016/j.stem.2008.09.015
– reference: 9) Yasunaga M, Tada S, Torikai-Nishikawa S, Nakano Y, Okada M, Jakt LM, Nishikawa S, Chiba T, Era T, Nishikawa S. Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 23(12): 1542-1550, 2005. Epub 2005 Nov 27
– reference: 21) Maehr R, Chen S, Snitow M, Ludwig T, Yagasaki L, Goland R, Leibel RL, Melton DA. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci USA 106(37): 15768-15773, 2009. doi: 10.1073/pnas. 0906894106 Epub 2009 Aug 31
– reference: 27) Hrvatin S, OʼDonnell CW, Deng F, Millman JR, Pagliuca FW, DiIorio P, Rezania A, Gifford DK, Melton DA. Differentiated human stem cells resemble fetal, not adult, b cells. Proc Natl Acad Sci USA 111 (8): 3038-3043,2014. doi: 10.1073/pnas.1400709111 Epub 2014 Feb 10
– reference: 22) Tateishi K, He J, Taranova O, Liang G, DʼAlessio AC,Zhang Y. Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem 283 (46): 31601-31607, 2008. doi: 10.1074/jbc.M806597200 Epub 2008 Sep 9
– reference: 11) Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG,Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, DʼAmour KA, Carpenter MK, Baetge EE. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26 (4): 443-452, 2008. doi:10.1038/nbt1393 Epub 2008 Feb 20
– reference: 37) Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N,Aoyama S, Adachi Y, Taniguchi H. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499(7459): 481-484, 2013. doi: 10. 1038/nature12271 Epub 2013 Jul 3
– reference: 7) Gradwohl G, Dierich A, LeMeur M, Guillemot F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci USA 97(4): 1607-1611, 2000
– reference: 12) Chen S, Borowiak M, Fox JL, Maehr R, Osafune K, Davidow L, Lam K, Peng LF, Schreiber SL, Rubin LL,Melton D. A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol 5 (4): 258-265, 2009. doi: 10.1038/nchembio. 154 Epub 2009 Mar 15
– reference: 10) DʼAmour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD,Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24 (11): 1392-1401, 2006. Epub 2006 Oct 19
– reference: 28) Teo AK, Wagers AJ, Kulkarni RN. New opportunities: harnessing induced pluripotency for discovery in diabetes and metabolism. Cell Metab 18(6): 775-791, 2013. doi:10.1016/j.cmet.2013.08.010 Epub 2013 Sep 12
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Snippet 膵β細胞は, 唯一の血糖降下作用ホルモンであるインスリンを分泌する細胞である. この膵β細胞が喪失し, インスリンが枯渇する糖尿病患者に対する根治療法として膵・膵島移植が行われている. しかしながら, 膵・膵島移植はドナー数不足という問題を抱えており, これを解決しうる方法の一つとして再生医療が期待されている....
SourceID medicalonline
jstage
SourceType Publisher
StartPage 228
SubjectTerms インスリン
人工多能性幹細胞(iPS 細胞)
糖尿病
胚性幹細胞(ES 細胞)
膵β 細胞
Title 多能性幹細胞を用いた 膵 β 細胞分化誘導研究の最新動向
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