Evaluation of Pancreatic β-cell Differentiation Efficiency of Human iPSC Lines for Clinical Use


如何引用文章

全文:

详细

Background:Transplantation of pancreatic β-cells generated from human induced pluripotent stem cells (hiPSCs) has great potential as a root treatment for type 1 diabetes. However, their current level of efficiency to differentiate into β-cells is still not at par for clinical use. Previous research has shown that differentiation efficiency varies among human embryonic stem cells and mouse-induced pluripotent stem cell lines. Therefore, selecting a suitable cell line for efficient induction into desired tissues and organs is crucial.

Methods:In this study, we have evaluated the efficiency of 15 hiPSC lines available for clinical use to differentiate into pancreatic β-cells.

Results:Our investigation has revealed induction efficiency to differ among the hiPSC lines, even when derived from the same donor. Among the hiPSC lines tested, the 16A01 cell line exhibited the highest insulin expression and low glucagon expression, suggesting that this cell line is suitable for differentiation into β-cells.

Conclusion:Our study has demonstrated the importance of selecting a suitable hiPSC line for effective differentiation into β-cells.

作者简介

Ayumi Horikawa

Department of Life Sciences (Biology), Graduate School of Arts and Sciences, University of Tokyo

Email: info@benthamscience.net

Kyoko Tsuda

Department of Life Sciences (Biology), Graduate School of Arts and Sciences, University of Tokyo

Email: info@benthamscience.net

Takayoshi Yamamoto

Department of Life Sciences (Biology), Graduate School of Arts and Sciences, University of Tokyo

Email: info@benthamscience.net

Tatsuo Michiue

Department of Life Sciences (Biology), Graduate School of Arts and Sciences, University of Tokyo

编辑信件的主要联系方式.
Email: info@benthamscience.net

参考

  1. Foster, N.C.; Beck, R.W.; Miller, K.M.; Clements, M.A.; Rickels, M.R.; DiMeglio, L.A.; Maahs, D.M.; Tamborlane, W.V.; Bergenstal, R.; Smith, E.; Olson, B.A.; Garg, S.K. State of type 1 diabetes management and outcomes from the T1D exchange in 2016–2018. Diabetes Technol. Ther., 2019, 21(2), 66-72. doi: 10.1089/dia.2018.0384 PMID: 30657336
  2. Miller, K.M.; Hermann, J.; Foster, N.; Hofer, S.E.; Rickels, M.R.; Danne, T.; Clements, M.A.; Lilienthal, E.; Maahs, D.M.; Holl, R.W.; Weinstock, R.; Izquierdo, R.; Sheikh, U.; Conboy, P.; Bulger, J.; Bzdick, S.; Klingensmith, G.; Banion, C.; Barker, J.; Cain, C.; Nadeau, K.; Rewers, M.; Rewers, A.; Slover, R.; Steck, A.; Wadwa, P.; Zeitler, P.; Alonso, G.; Forlenza, G.; Gerard-Gonzalez, A.; Green, M.; Gross, S.; Majidi, S.; Messer, L.; Reznick-Lipina, T.; Simmons, E.; Thivener, K.; Weber, I.; Willi, S.; Lipman, T.; Kucheruk, O.; Minnock, P.; Carchidi, C.; Grant, B.; Olivos, D.; DiMeglio, L.; Hannon, T.; Evans-Molina, C.; Hansen, D.; Pottorff, T.; Woerner, S.; Hildinger, M.; Hufferd, R.; Newnum, A.; Purtlebaugh, D.; Smith, L.; Wendholt, K.; Goland, R.; Gandica, R.; Williams, K.; Pollack, S.; Casciano, E.; Hochberg, J.; Uche, C.; Lee, J.; Gregg, B.; Tan, M.; Ang, L.; Pop-Busui, R.; Thomas, I.; Dhadphale, E.; Dominowski, J.; Garrity, A.; Leone, V.; Plunkett, C.; Plunkett, B.; Monzavi, R.; Cheung, C.; Fisher, L.; Kim, M.; Miyazaki, B.; Pitukcheewanont, P.; Sandstrom, A.; Austin, J.; Change, N.; Raymond, J.; Ichihara, B.; Lipton, M.; Flores Garcia, J.; Garg, S.; Michels, A.; Garcetti, R.; Green, M.; Gutin, R.; Nadeau, K.; Polsky, S.; Shah, V.; Voelmle, M.; Myers, L.; Coe, G.; Demmitt, J.; Garcia Reyes, Y.; Giordano, D.; Joshee, P.; Nease, E.; Nguyen, N.; Wolfsdorf, J.; Quinn, M.; Fontanet, C.; Mukherjee, S.; Bethin, K.; Quattrin, T.; Majumdar, I.; Mastrandrea, L.; Gorman, E.; House, A.; Michalovic, S.; Musial, W.; Shine, B.; Ahmann, A.; Castle, J.; Joarder, F.; Aby-Daniel, D.; Guttmann-Bauman, I.; Klopfenstein, B.; Morimoto, V.; Cady, N.; Fitch, R.; DeFrang, D.; Jahnke, K.; Patoine, C.; Raman, V.; Foster, C.; Murray, M.; Brown, T.; Davis, C.; Slater, H.; Langvardt, J.; Bode, B.; Boyd, J.; Johnson, J.; Newton, C.; Ownby, J.; Hosey, R.S.; Rastogi, N.; Winslett, B.; Hirsch, I.; DeSantis, A.; Failor, R.A.; Greenbaum, C.; Trence, D.; Trikudanathan, S.; Khakpour, D.; Thomson, P.; Sameshima, L.; Tordillos, C.; Clements, M.; Turpin, A.; Babar, G.; Broussard, J.; Cernich, J.; Dileepan, K.; Feldt, M.; Moore, W.; Musick, T.; Patton, S.; Yan, Y.; Tsai, S.; Bedard, J.; Elrod, A.; Hester, L.; Beidelschies, M.; de la Garza, J.; Haith, E.; James, J.; Ramey, E.; Slover, J.; Valentine, A.; Watkins, D.; Whisenhunt, M.; Wierson, J.; Wilson, D.; Buckingham, B.; Maahs, D.; Prahalad, P.; Hsu, L.; Kingman, R.; Tabatabai, I.; Liljenquist, D.; Sulik, M.; Vance, C.; Halford, J.; Funke, C.; Appiagyei-Dankah, Y.; Beltz, E.; Moran, K.; Starkman, H.; Cerame, B.; Chin, D.; Ebner-Lyon, L.; Sabanosh, K.; Silverman, L.; Wagner, C.; Cheruvu, S.; Fox, M.; Melchionne, F.; Bergenstal, R.; Madden, M.; Martens, T.; Criego, A.; Powers, M.; Carlson, A.; Beasley, S.; Olson, B.; Thomas, L.A.; McCann, K.; Dunnigan, S.; Ashanti, C.; Simmons, J.; Russell, W.; Jaser, S.; Kelley, J.; Brendle, F.; Williams, L.; Savin, K.; Flowers, K.; Williams, G.; Hamburger, E.; Davis, A.; Hammel, B.; Cengiz, E.; Tamborlane, W.; Weyman, K.; Van Name, M.; Patel, N.; Sherr, J.; Tichy, E.; Steffen, A.; Zgorski, M.; Carria, L.; Finnegan, J.; Duran, E.; Mehta, S.; Katz, M.; Laffel, L.; Giani, E.; Snelgrove, R.; Hanono, A.; Commissariat, P.; Griffith, J.; Atkins, A.; Harrington, K.; Kim, K.; Masclans, L.; Naik, N.; Ambler-Osborn, L.; Schultz, A.; Cohen, C.; Anderson, B.; McGill, J.; Granados, A.; Clifton, M.J.; Hurst, S.; Kissel, S.; Recklein, C.; Kruger, D.; Bhan, A.; Brown, T.; Tassopoulos, A.; Hailey, A.; Remtema, H.; Cushman, T.; Wintergerst, K.; Watson, S.; Kingery, S.; Rayborn, L.; Rush, H.; Foster, M.; Deuser, A.; Rodriguez-Luna, M.; Eubanks, S.; Rodriguez, H.; Bollepalli, S.; Smith, L.; Shulman, D.; Jorgensen, E.V.; Eyth, E.; Brownstein, R.; Rodriguez, J.; O’Bria, J.; Aleppo-Kacmarek, G.; Hahr, A.; Molitch, M.; Muayed, E.; Toft, D.; Fulkerson, C.; Adelman, D.; Massaro, E.; Webb, K.; Peters, A.; Ruelas, V.; Harmel, M.; Daniels, M.; Forghani, N.; Flannery, T.; Reh, C.; Bhangoo, A.; Kashmiri, H.; Montgomery, K.; Trinh, L.; Speer, H.; Lane, K.; Bergenstal, R.; Martens, T.; Madden, M.; Powers, M.; Criego, A.; Carlson, A.; Olson, B.; Beasley, S.; McCann, K.; Thomas, L.A.; Miller, C.; Ashanti, C.; Solorzano, C.B.; Puskaric, J.; Benjamin, R.; Adkins, D.; Spruill, A.; Williams, C.; Tsalikian, E.; Tansey, M.; Bansl, N.; Cabbage, J.; Coffey, J.; Schatz, D.; Clare-Salzler, M.; Cusi, K.; Fudge, B.; Haller, M.; Meehan, C.; Rohrs, H.; Silverstein, J.; Walker, A.; Albanese-O’Niell, A.; Foss, S.; Adams, J.; Cintron, M.; Thomas, N.; Gottschalk, M.; Newfield, R.; Hashiguchi, M.; Sparling, D.; Tryggested, J.; Beck, J.; Less, J.; Weber, L.; Adi, S.; Gitelman, S.; Sanda, S.; Wong, J.; McDonnell, M.; Mueller, M.; Izadi, Z.; Mistry, S.; Nelson, B.; Looper, L.; Frost, C.; Redondo, M.; Lyons, S.; Klinepeter, S.; Fegan-Bohm, K.; Bacha, F.; DeSalvo, D.; Butler, A.; Hilliard, M.; Khetani, F.; Yulatic, R.; Hudson, R.; Irvine, L.; Zubair, S.; Pace, C.; Pitrello, A.; Levy, W.; Njoku, C.; Zipf, W.; Dyer, J.; Lozano, R.; Seiple, D.; Corven, G.; Jaycox, M.; Wood, J.; Macleish, S.; Gubitosi-Klug, R.; Adams, R.; McGuigan, P.; Casey, T.; Campbell, W.; Kittelsrud, J.; Gupta, A.; Peterson, V.; Libman, I.; Diaz, A.; Jelley, D.; Crowder, C.; Greer, D.; Crawford, J.; Goudeau, S.; Pihoker, C.; Yi-Frazier, J.; Kearns, S.; Pascual, M.; Loots, B.; Beauregard, N.; Rickels, M.; O’Brien, S.; Agarwal, S.; Peleckis, A.; Dalton-Bakes, C.; Markmann, E.; Umpierrez, G.; Muir, A.; Ramos, C.; Behbahani, K.; Dhruv, N.; Gartzman, N.; Nathan, B.; Bellin, M.; Sunni, M.; Flaherty, N.; Leschyshyn, J.; Schmid, K.; Weingartner, D.; Ludwig, M.; Nelson, B.; Kogler, A.; Bartyzal, A.; Street, A.; Pappenfus, B.; Sweet, J.; Buse, J.; Young, L.; Bergamo, K.; Goley, A.; Kirkman, M.; Diner, J.; Kass, A.; Dezube, M.; Arnold, K.; Evans, T.; Sellers, S.; Blackman, S.; Abel, K-L.; Rasbach, L.; Ali, O.; Wolfgram, P.; Fiallo-Sharer, R.; Kramer, J.; Beesley, C.; Bingham-Tyson, C.; Unteutsh, R.; Harlan, D.; Lee, M.; Soyka, L.; Feldman, P.; Thompson, M.; Gallagher-Dorval, K.; Hubacz, L.; Hartigan, C.; Ciccarelli, C.; Edelen, R.; Edelen, M.; Borgwadt, T.; Stauffacher, K.; DeGrote, K.; Gruetzmacher, C.; Shepperd, M.; Bhargava, A.; Wright, D.; Fitzgerald, K.; Khoo, T.; Young, N.; Borg, L.; Stifel, K.; Rail, C.; Casas, L.; Eidenshink, E.; Huber, C.; Rieder, A.; Tuchscherer, A.; Broadbent, M.; Dolan, L.; Corathers, S.; Kichler, J.; Sheanon, N.; Baugh, H.; Standiford, D.; Weis, T.; Fox, C.; Schultz, C.; Ritter, A.; Vendrame, F.; Blashke, C.; Matheson, D.; Sanders-Branca, N.; Rudolph, J.; Biersdorf, D.; Fitch-Danielson, J.; Eckerle-Mize, D.; Brendle, F.; Fry, J.; Davis, D.; Lovell, C.; Hammel, B.; Williams, L.; Hoffman, R.; Chaudhari, M.; Kamboj, M.; Carr, L.; Casas, L.; Blehm, J.; Tello, A.; Walter, J.A.; Ward, R.; Broadbent, M.; Blomquist, G.; Stewart, M.; Cross, P.; Racki, S.; Sterchi, L.; Gouine, D.; Kiesow, B.; Welch, S.; Philis-Tsimikas, A.; Daily, G.; Chang, A.; McCallum, J.; Garcia, I.; Vela, T.; Loupasi, I.; Rosal, R.; Toschi, E.; Middelbeek, R.; Munshi, M.; Slyne, C.; Atakov-Castillo, A.; Fox, L.; Mauras, N.; Wasserman, R.; Damaso, L.; Englert, K.; Sikes, K.; Ponthieux, K.; Phillipson, L.; Cohen, A.; Gannon, G.; Deeb, L.; Shiver, A.; Schroeder, L.; Schworm, W.; Graham, K.; Levy, C.; Lam, D.; Burtman, E.; Levister, C.; Ogyaadu, S.; Gassner, H.; Duke, J.; Touger, L.; Newbern, D.; Hoekstra, F.; Harwood, K.; Prasad, V.; Daguanno, J.A.; Pratley, R.; Corbin, K.; Wright, M.; Nagel, S.; Water, N.; Ghere, M.; Whitaker, K.; Heptulla, R.; Katikaneni, R.; Johnson-Newell, D.; Crandall, J.; Powell, D.; Anghel, V.; Ghanny, S.; Aisenberg, J.; Chartoff, A.; Sivitz, J.; Mathus, S.; Cospito, T-L.; Thailkill, K.; Fowlkes, J.; Kalaitzoglou, E.; Morales Pozzo, A.; Edwards, K. Longitudinal changes in continuous glucose monitoring use among individuals with type 1 Diabetes: International comparison in the German and Austrian DPV and U.S. T1D exchange registries. Diabetes Care, 2020, 43(1), e1-e2. doi: 10.2337/dc19-1214 PMID: 31672703
  3. Posselt, A.M.; Szot, G.L.; Frassetto, L.A.; Masharani, U.; Tavakol, M.; Amin, R.; McElroy, J.; Ramos, M.D.; Kerlan, R.K.; Fong, L.; Vincenti, F.; Bluestone, J.A.; Stock, P.G. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation, 2010, 90(12), 1595-1601. doi: 10.1097/TP.0b013e3181fe1377 PMID: 20978464
  4. Barton, F.B.; Rickels, M.R.; Alejandro, R.; Hering, B.J.; Wease, S.; Naziruddin, B.; Oberholzer, J.; Odorico, J.S.; Garfinkel, M.R.; Levy, M.; Pattou, F.; Berney, T.; Secchi, A.; Messinger, S.; Senior, P.A.; Maffi, P.; Posselt, A.; Stock, P.G.; Kaufman, D.B.; Luo, X.; Kandeel, F.; Cagliero, E.; Turgeon, N.A.; Witkowski, P.; Naji, A.; O’Connell, P.J.; Greenbaum, C.; Kudva, Y.C.; Brayman, K.L.; Aull, M.J.; Larsen, C.; Kay, T.W.H.; Fernandez, L.A.; Vantyghem, M.C.; Bellin, M.; Shapiro, A.M.J. Improvement in outcomes of clinical islet transplantation: 1999-2010. Diabetes Care, 2012, 35(7), 1436-1445. doi: 10.2337/dc12-0063 PMID: 22723582
  5. Russ, H.A.; Parent, A.V.; Ringler, J.J.; Hennings, T.G.; Nair, G.G.; Shveygert, M.; Guo, T.; Puri, S.; Haataja, L.; Cirulli, V.; Blelloch, R.; Szot, G.L.; Arvan, P.; Hebrok, M. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J., 2015, 34(13), 1759-1772. doi: 10.15252/embj.201591058 PMID: 25908839
  6. Rezania, A.; Bruin, J.E.; Arora, P.; Rubin, A.; Batushansky, I.; Asadi, A.; O’Dwyer, S.; Quiskamp, N.; Mojibian, M.; Albrecht, T.; Yang, Y.H.C.; Johnson, J.D.; Kieffer, T.J. Reversal of diabetes with Insulin-producing cells derived in vitro from human pluripotent stem cells. Nat. Biotechnol., 2014, 32(11), 1121-1133. doi: 10.1038/nbt.3033 PMID: 25211370
  7. Yabe, S.G.; Fukuda, S.; Takeda, F.; Nashiro, K.; Shimoda, M.; Okochi, H. Efficient generation of functional pancreatic β-cells from human induced pluripotent stem cells. J. Diabetes, 2017, 9(2), 168-179. doi: 10.1111/1753-0407.12400 PMID: 27038181
  8. Yabe, S.G.; Fukuda, S.; Nishida, J.; Takeda, F.; Nashiro, K.; Okochi, H. Induction of functional islet-like cells from human iPS cells by suspension culture. Regen. Ther., 2019, 10, 69-76. doi: 10.1016/j.reth.2018.11.003 PMID: 30623004
  9. Raikwar, S.P.; Kim, E.M.; Sivitz, W.I.; Allamargot, C.; Thedens, D.R.; Zavazava, N. Human iPS cell-derived Insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice. PLoS One, 2015, 10(1), e0116582. doi: 10.1371/journal.pone.0116582 PMID: 25629318
  10. Umekage, M.; Sato, Y.; Takasu, N. Overview: An iPS cell stock at CiRA. Inflamm. Regen., 2019, 39(1), 17. doi: 10.1186/s41232-019-0106-0 PMID: 31497180
  11. Hanatani, T.; Takasu, N. CiRA iPSC seed stocks (CiRA’s iPSC Stock Project). Stem Cell Res., 2021, 50, 102033. doi: 10.1016/j.scr.2020.102033 PMID: 33445065
  12. Yoshida, S.; Kato, T.M.; Sato, Y.; Umekage, M.; Ichisaka, T.; Tsukahara, M.; Takasu, N.; Yamanaka, S. A clinical-grade HLA haplobank of human induced pluripotent stem cells matching approximately 40% of the Japanese population. Med, 2023, 4(1), 51-66.e10. doi: 10.1016/j.medj.2022.10.003 PMID: 36395757
  13. Kim, S.E.; Kim, B.K.; Gil, J.E.; Kim, S.K.; Kim, J.H. Comparative analysis of the developmental competence of three human embryonic stem cell lines in vitro. Mol. Cells, 2007, 23(1), 49-56. PMID: 17464211
  14. Osafune, K.; Caron, L.; Borowiak, M.; Martinez, R.J.; Fitz-Gerald, C.S.; Sato, Y.; Cowan, C.A.; Chien, K.R.; Melton, D.A. Marked differences in differentiation propensity among human embryonic stem cell lines. Nat. Biotechnol., 2008, 26(3), 313-315. doi: 10.1038/nbt1383 PMID: 18278034
  15. Pringle, S.; De Bari, C.; Dell’Accio, F.; Przyborski, S.; Cooke, M.J.; Minger, S.L.; Grigoriadis, A.E. Mesenchymal differentiation propensity of a human embryonic stem cell line. Cell Prolif., 2011, 44(2), 120-127. doi: 10.1111/j.1365-2184.2011.00744.x PMID: 21401753
  16. Wu, H.; Xu, J.; Pang, Z.P.; Ge, W.; Kim, K.J.; Blanchi, B.; Chen, C.; Südhof, T.C.; Sun, Y.E. Integrative genomic and functional analyses reveal neuronal subtype differentiation bias in human embryonic stem cell lines. Proc. Natl. Acad. Sci. USA, 2007, 104(34), 13821-13826. doi: 10.1073/pnas.0706199104 PMID: 17693548
  17. Martinez Arias, A.; Brickman, J.M. Gene expression heterogeneities in embryonic stem cell populations: Origin and function. Curr. Opin. Cell Biol., 2011, 23(6), 650-656. doi: 10.1016/j.ceb.2011.09.007 PMID: 21982544
  18. Cahan, P.; Daley, G.Q. Origins and implications of pluripotent stem cell variability and heterogeneity. Nat. Rev. Mol. Cell Biol., 2013, 14(6), 357-368. doi: 10.1038/nrm3584 PMID: 23673969
  19. Hayashi, Y.; Ohnuma, K.; Furue, M.K. Pluripotent stem cell heterogeneity. In: Stem cells heterogeneity - Novel concepts. Advances in experimental medicine and biology; Birbrair, A., Ed.; Springer: Cham, 2019; vol 1123, pp. 71-94. doi: 10.1007/978-3-030-11096-3_6
  20. Yang, S.; Cho, Y.; Jang, J. Single cell heterogeneity in human pluripotent stem cells. BMB Rep., 2021, 54(10), 505-515. doi: 10.5483/BMBRep.2021.54.10.094 PMID: 34488931
  21. Ohno, Y.; Yuasa, S.; Egashira, T.; Seki, T.; Hashimoto, H.; Tohyama, S.; Saito, Y.; Kunitomi, A.; Shimoji, K.; Onizuka, T.; Kageyama, T.; Yae, K.; Tanaka, T.; Kaneda, R.; Hattori, F.; Murata, M.; Kimura, K.; Fukuda, K. Distinct iPS cells show different cardiac differentiation efficiency. Stem Cells Int., 2013, 2013, 1-11. doi: 10.1155/2013/659739 PMID: 24367382
  22. Ninomiya, H.; Mizuno, K.; Terada, R.; Miura, T.; Ohnuma, K.; Takahashi, S.; Asashima, M.; Michiue, T. Improved efficiency of definitive endoderm induction from human induced pluripotent stem cells in feeder and serum-free culture system. In vitro Cell. Dev. Biol. Anim., 2015, 51(1), 1-8. doi: 10.1007/s11626-014-9801-y PMID: 25124871
  23. Horikawa, A.; Mizuno, K.; Tsuda, K.; Yamamoto, T.; Michiue, T. A simple method of hiPSCs differentiation into Insulin-producing cells is improved with vitamin C and RepSox. PLoS One, 2021, 16(7), e0254373. doi: 10.1371/journal.pone.0254373 PMID: 34252142
  24. Takahashi, K.; Tanabe, K.; Ohnuki, M.; Narita, M.; Ichisaka, T.; Tomoda, K.; Yamanaka, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 2007, 131(5), 861-872. doi: 10.1016/j.cell.2007.11.019 PMID: 18035408
  25. Ohnuki, M.; Takahashi, K.; Yamanaka, S. Generation and characterization of human induced pluripotent stem cells. Curr. Protoc. Stem Cell Biol., 2009, 9(1), 2. doi: 10.1002/9780470151808.sc04a02s9 PMID: 19536759
  26. Zhu, Y.; Liu, Q.; Zhou, Z.; Ikeda, Y. PDX1, Neurogenin-3, and MAFA: Critical transcription regulators for beta cell development and regeneration. Stem Cell Res. Ther., 2017, 8(1), 240. doi: 10.1186/s13287-017-0694-z PMID: 29096722
  27. Yang, Y.; Wang, H.; He, J.; Shi, W.; Jiang, Z.; Gao, L.; Jiang, Y.; Ni, R.; Yang, Q.; Luo, L. A single-cell–resolution fate map of endoderm reveals demarcation of pancreatic progenitors by cell cycle. Proc. Natl. Acad. Sci. USA, 2021, 118(25), e2025793118. doi: 10.1073/pnas.2025793118 PMID: 34161274
  28. Krentz, N.A.J.; van Hoof, D.; Li, Z.; Watanabe, A.; Tang, M.; Nian, C.; German, M.S.; Lynn, F.C. Phosphorylation of NEUROG3 links endocrine differentiation to the cell cycle in pancreatic progenitors. Dev. Cell, 2017, 41(2), 129-142.e6. doi: 10.1016/j.devcel.2017.02.006 PMID: 28441528
  29. Ning, H.; Horikawa, A.; Yamamoto, T.; Michiue, T. Chemical inhibitors of cyclin-dependent kinase (CDKi) improve pancreatic endocrine differentiation of iPS cells. In vitro Cell Dev Biol Anim 2023, 59, 410-419. doi: 10.1007/s11626-023-00776-0
  30. Aigha, I.I.; Abdelalim, E.M. NKX6.1 transcription factor: A crucial regulator of pancreatic β cell development, identity, and proliferation. Stem Cell Res. Ther., 2020, 11(1), 459. doi: 10.1186/s13287-020-01977-0 PMID: 33121533
  31. Memon, B.; Younis, I.; Abubaker, F.; Abdelalim, E.M. PDX1 − /NKX6.1 + progenitors derived from human pluripotent stem cells as a novel source of Insulin-secreting cells. Diabetes Metab. Res. Rev., 2021, 37(5), e3400. doi: 10.1002/dmrr.3400 PMID: 32857429
  32. Paget, M.B.; Murray, H.E.; Bailey, C.J.; Flatt, P.R.; Downing, R. Rotational co-culture of clonal β-cells with endothelial cells: Effect of PPAR-γ agonism in vitro on Insulin and VEGF secretion. Diabetes Obes. Metab., 2011, 13(7), 662-668. doi: 10.1111/j.1463-1326.2011.01392.x PMID: 21435140
  33. Sabra, G.; Vermette, P. A 3D cell culture system: Separation distance between INS-1 cell and endothelial cell monolayers co-cultured in fibrin influences INS-1 cells Insulin secretion. Biotechnol. Bioeng., 2013, 110(2), 619-627. doi: 10.1002/bit.24716 PMID: 22949028
  34. Kroon, E.; Martinson, L.A.; Kadoya, K.; Bang, A.G.; Kelly, O.G.; Eliazer, S.; Young, H.; Richardson, M.; Smart, N.G.; Cunningham, J.; Agulnick, A.D.; D’Amour, K.A.; Carpenter, M.K.; Baetge, E.E. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive Insulin-secreting cells in vivo. Nat. Biotechnol., 2008, 26(4), 443-452. doi: 10.1038/nbt1393 PMID: 18288110
  35. Ramzy, A.; Thompson, D.M.; Ward-Hartstonge, K.A.; Ivison, S.; Cook, L.; Garcia, R.V.; Loyal, J.; Kim, P.T.W.; Warnock, G.L.; Levings, M.K.; Kieffer, T.J. Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes. Cell Stem Cell, 2021, 28(12), 2047-2061.e5. doi: 10.1016/j.stem.2021.10.003 PMID: 34861146

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Bentham Science Publishers, 2024