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Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo
Abstract
Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implanted mice, human insulin and C-peptide are detected in sera at levels similar to those of mice transplanted with approximately 3,000 human islets. Moreover, the insulin-expressing cells generated after engraftment exhibit many properties of functional beta-cells, including expression of critical beta-cell transcription factors, appropriate processing of proinsulin and the presence of mature endocrine secretory granules. Finally, in a test of therapeutic potential, we demonstrate that implantation of hES cell-derived pancreatic endoderm protects against streptozotocin-induced hyperglycemia. Together, these data provide definitive evidence that hES cells are competent to generate glucose-responsive, insulin-secreting cells.
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“In particular, ViaCyte developed a stem cell-derived pancreatic endoderm cell population known as PEC-01, which they demonstrated to mature over several months in vivo into insulin-producing endocrine cells in rodent models.29–31”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [31]
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Brissova, M., Fowler, M. J., Nicholson, W. E., Chu, A., Hirshberg, B., Harlan, D. M., & Powers, A. C. (2005) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.5c6684.2005 · Cited by 797
Successful Islet Transplantation
Ryan, E. A., Lakey, J. R. T., Paty, B. W., Imes, S., Korbutt, G. S., Kneteman, N. M., Bigam, D., Rajotte, R. V., & Shapiro, A. M. J. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2148 · Cited by 719
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Research works printed but not linked: 43
- Lakey, J.R., Mirbolooki, M. & Shapiro, A.M. Current status of clinical islet cell transplantation. Methods Mol. Biol. 333, 47–104 (2006).
- Amit, M. et al. Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev. Biol. 227, 271–278 (2000). · DOI
- Rosler, E.S. et al. Long-term culture of human embryonic stem cells in feeder-free conditions. Dev. Dyn. 229, 259–274 (2004). · DOI
- D'Amour, K.A. et al. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat. Biotechnol. 23, 1534–1541 (2005). · DOI · Paper page
- D'Amour, K.A. et al. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat. Biotechnol. 24, 1392–1401 (2006). · DOI
- Jiang, J. et al. Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25, 1940–1953 (2007). · DOI
- Tuch, B.E., Osgerby, K.J. & Turtle, J.R. Reversal of diabetes in hyperglycaemic nude mice by human fetal pancreas. Transplant. Proc. 21, 2665–2666 (1989).
- Beattie, G.M., Butler, C. & Hayek, A. Morphology and function of cultured human fetal pancreatic cells transplanted into athymic mice: a longitudinal study. Cell Transplant. 3, 421–425 (1994). · DOI
- Hayek, A. & Beattie, G.M. Experimental transplantation of human fetal and adult pancreatic islets. J. Clin. Endocrinol. Metab. 82, 2471–2475 (1997).
- Castaing, M. et al. Blood glucose normalization upon transplantation of human embryonic pancreas into beta-cell-deficient SCID mice. Diabetologia 44, 2066–2076 (2001). · DOI
- Castaing, M., Duvillie, B., Quemeneur, E., Basmaciogullari, A. & Scharfmann, R. Ex vivo analysis of acinar and endocrine cell development in the human embryonic pancreas. Dev. Dyn. 234, 339–345 (2005). · DOI
- Jensen, J. Gene regulatory factors in pancreatic development. Dev. Dyn. 229, 176–200 (2004). · DOI
- Zorn, A.M. & Wells, J.M. Molecular basis of vertebrate endoderm development. Int. Rev. Cytol. 259, 49–111 (2007). · DOI
- Jorgensen, M.C. et al. An illustrated review of early pancreas development in the mouse. Endocr. Rev. 28, 685–705 (2007). · DOI
- Gaber, A.O. et al. Human islet graft function in NOD-SCID mice predicts clinical response in islet transplant recipients. Transplant. Proc. 36, 1108–1110 (2004). · DOI
- Cabrera, O. et al. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc. Natl. Acad. Sci. USA 103, 2334–2339 (2006). · DOI · Paper page
- Guz, Y. et al. Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. Development 121, 11–18 (1995). · DOI
- Collombat, P. et al. Embryonic endocrine pancreas and mature beta cells acquire alpha and PP cell phenotypes upon Arx misexpression. J. Clin. Invest. 117, 961–970 (2007). · DOI
- Olbrot, M., Rud, J., Moss, L.G. & Sharma, A. Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA. Proc. Natl. Acad. Sci. USA 99, 6737–6742 (2002). · DOI
- Matsuoka, T.A. et al. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol. Cell. Biol. 23, 6049–6062 (2003). · DOI
- Matsuoka, T.A. et al. The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. Proc. Natl. Acad. Sci. USA 101, 2930–2933 (2004). · DOI
- Nishimura, W. et al. A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells. Dev. Biol. 293, 526–539 (2006). · DOI
- Artner, I. et al. MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells. Diabetes 55, 297–304 (2006). · DOI
- Zhang, C. et al. MafA is a key regulator of glucose-stimulated insulin secretion. Mol. Cell. Biol. 25, 4969–4976 (2005). · DOI
- Wilson, M.E., Kalamaras, J.A. & German, M.S. Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive set of endocrine cells in the embryonic pancreas. Mech. Dev. 115, 171–176 (2002). · DOI
- Klimstra, D.S. in Histology for Pathologists. (ed. S.S. Sternberg) 613–647 (Lippincott-Raven Publishers, Philadelphia; 1997).
- Marzban, L. et al. Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death. Diabetes 55, 2192–2201 (2006). · DOI
- Okamoto, H. The role of poly(ADP-ribose) synthetase in the development of insulin-dependent diabetes and islet B-cell regeneration. Biomed. Biochim. Acta 44, 15–20 (1985).
- Eizirik, D.L. et al. Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury. Proc. Natl. Acad. Sci. USA 91, 9253–9256 (1994). · DOI
- Hosokawa, M., Dolci, W. & Thorens, B. Differential sensitivity of GLUT1- and GLUT2-expressing beta cells to streptozotocin. Biochem. Biophys. Res. Commun. 289, 1114–1117 (2001). · DOI
- Yang, H. & Wright, J.R., Jr. Human beta cells are exceedingly resistant to streptozotocin in vivo. Endocrinology 143, 2491–2495 (2002). · DOI
- Hering, B.J. et al. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. J. Am. Med. Assoc. 293, 830–835 (2005). · DOI
- Zertal-Zidani, S., Bounacer, A. & Scharfmann, R. Regulation of pancreatic endocrine cell differentiation by sulphated proteoglycans. Diabetologia 50, 585–595 (2007). · DOI
- Attali, M. et al. Control of beta-cell differentiation by the pancreatic mesenchyme. Diabetes 56, 1248–1258 (2007). · DOI
- Tulachan, S.S. et al. All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas. Diabetes 52, 76–84 (2003). · DOI
- Kobayashi, H. et al. Retinoid signaling controls mouse pancreatic exocrine lineage selection through epithelial-mesenchymal interactions. Gastroenterology 123, 1331–1340 (2002). · DOI
- Tuch, B.E. & Monk, R.S. Regulation of blood glucose to human levels by human fetal pancreatic xenografts. Transplantation 51, 1156–1160 (1991). · DOI
- Tuch, B.E., Jones, A. & Turtle, J.R. Maturation of the response of human fetal pancreatic explants to glucose. Diabetologia 28, 28–31 (1985). · DOI
- Tuch, B.E. Reversal of diabetes by human fetal pancreas. Optimization of requirements in the hyperglycemic nude mouse. Transplantation 51, 557–562 (1991). · DOI
- Fornoni, A. et al. Inhibition of c-jun N terminal kinase (JNK) improves functional beta cell mass in human islets and leads to AKT and glycogen synthase kinase-3 (GSK-3) phosphorylation. Diabetologia 51, 298–308 (2008). · DOI
- Weitgasser, R., Davalli, A.M. & Weir, G.C. Measurement of glucose concentrations in rats: differences between glucose meter and plasma laboratory results. Diabetologia 42, 256 (1999). · DOI
- Joannides, A. et al. Automated mechanical passaging: a novel and efficient method for human embryonic stem cell expansion. Stem Cells 24, 230–235 (2006). · DOI
- Schrot, R.J., Patel, K.T. & Foulis, P. Evaluation of inaccuracies in the measurement of glycemia in the laboratory, by glucose meters, and through measurement of hemoglobin A1c. Clin Diabetes 25, 43–49 (2007). · DOI
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Self-citationLineage determinants in early endocrine development
Rieck, S., Bankaitis, E. D., & Wright, C. V. E. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.06.005 · Cited by 56
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BackgroundThe science and ethics of induced pluripotency: what will become of embryonic stem cells?
Zacharias, D. G., Nelson, T. J., Mueller, P. S., & Hook, C. (2011) · Mayo Clinic proceedings · doi:10.4065/mcp.2011.0054 · Cited by 56
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Liu, K., Chen, Y., Xie, M., Li, K., & Ding, S. (2016) · Cell chemical biology · doi:10.1016/j.chembiol.2016.07.007 · Cited by 60
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“This is particularly relevant, as uncontrolled differentiation and growth, so-called teratomas, have often been observed in mice grafted with stem cell-derived pancreatic precursors (Kroon et al , 2008; Kelly et al , 2011).”
Liu, H., Yang, H., Zhu, D., Sui, X. Y., Li, J., Liang, Z., Xu, L., Chen, Z., Yao, A., Zhang, L., et al. (2014) · Cell Research · doi:10.1038/cr.2014.118 · Cited by 53
Pluripotent Stem Cells as a Potential Tool for Disease Modelling and Cell Therapy in Diabetes
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Liao, X., Xue, H., Wang, Y.-C., Nazor, K. L., Guo, S., Trivedi, N. S., Peterson, S. E., Liu, Y. M., Loring, J. F., & Laurent, L. C. (2013) · Journal of Cell Science · doi:10.1242/jcs.123570 · Cited by 56
“…and small molecules, beta isletlike cells can be obtained from hESCs using a five-stage protocol: (1) definitive endoderm (DE); (2) primitive gut tube; (3) posterior foregut; (4) pancreatic progenitor; and (5) pancreatic endoderm (D’Amour et al., 2006; Kroon et al., 2008; Van Hoof et al., 2009).”
BackgroundMethodBell, G. I., Meschino, M. T., Hughes-Large, J. M., Broughton, H. C., Xenocostas, A., & Hess, D. A. (2012) · Stem Cells and Development · doi:10.1089/scd.2011.0634 · Cited by 51
Pancreatic islet and progenitor cell surface markers with cell sorting potential
Hald, J., Galbo, T., Rescan, C., Radzikowski, L., Sprinkel, A. E., Heimberg, H., Ahnfelt‐Rønne, J., Jensen, J. N., Scharfmann, R., Gradwohl, G., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2295-1 · Cited by 55
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BackgroundFu, X., & Xu, Y. (2012) · Genome Medicine · doi:10.1186/gm354 · Cited by 55
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BackgroundRgs16 and Rgs8 in embryonic endocrine pancreas and mouse models of diabetes
Villasenor, A., Wang, Z. V., Rivera, L. B., Ocal, O., Asterholm, I. W., Scherer, P. E., Brekken, R. A., Cleaver, O. B., & Wilkie, T. M. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.003210 · Cited by 52
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BackgroundA Gutsy Task: Generating Intestinal Tissue from Human Pluripotent Stem Cells
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Plank, J. L., Mundell, N. A., Frist, A., LeGrone, A., Kim, T., Musser, M. A., Walter, T. J., & Labosky, P. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.11.013 · Cited by 53
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“This resulted in significant improvements in the specification efficiency, as well as the prevention of streptozotocininduced diabetes.(90) At that point, Viacyte announced their intention to submit an investigational new drug application for their product proislet, which basically consists of human ES cells partially…”
BackgroundGeneration of islet-like cells from mouse gall bladder by direct ex vivo reprogramming
Hickey, R., Galivo, F., Schug, J., Brehm, M. A., Haft, A., Wang, Y., Benedetti, E., Gu, G., Magnuson, M. A., Shultz, L. D., et al. (2013) · Stem Cell Research · doi:10.1016/j.scr.2013.02.005 · Cited by 50
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“were able to differentiate insulin-expressing cells from human ES cells [24] that could respond to glucose in vivo and could be used to successfully treat diabetic mice, suggesting that they were functionally glucose responsive [40].”
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Al‐Khawaga, S., Memon, B., Butler, A. E., Taheri, S., Abou‐Samra, A., & Abdelalim, E. M. (2017) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12349 · Cited by 59
“This stage is recognized by the expression of specific markers such as SOX17, FOXA2, C-X-C chemokine receptor type 4 (CXCR4), and GSC (D’Amour et al., 2005; Jiang et al., 2007a; Kroon et al., 2008; Johannesson et al., 2009; Zhang et al., 2009a; Mfopou et al., 2010) (Fig.”
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“cultures of liver hepatocytes and pancreatic endocrine cells that have therapeutic efficacy in animal models of liver disease and diabetes((83)), respectively.”
BackgroundMontanucci, P., Basta, G., Pescara, T., Pennoni, I., Giovanni, F. D., & Calafiore, R. (2011) · Tissue Engineering. Part A · doi:10.1089/ten.tea.2010.0587 · Cited by 50
“In fact, hES need an appropriate treatment with factors like Wnt 56 to reach a degree of differentiation that may approach our re-sults.”
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Hakim, F., Kaitsuka, T., Raeed, J. M., Wei, F.-Y., Shiraki, N., Akagi, T., Yokota, T., Kume, S., & Tomizawa, K. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.524363 · Cited by 49
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“RA signaling plays a critical role in pancreas specification and is a key component of in vitro protocols inducing human ES cells into β cells.(10,11,43) Pharmacological(42,44) (DEAB or BMS493) or genetic (raldh2 mutant) disruption of RA signaling in zebrafish leads to a loss of both pancreas and liver progenitors; ho…”
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“Derivation of Endodermal Cells from hESCs Cirrhosis, Hepatocellular carcinoma, Diabetes- associated liver disease Hepatocytes Differentiation of hESC into definitive endoderm, followed by sequential exposure to differentiation factors FGF, BMP4 hepatocyte growth factor oncostatin M dexamethasone [35, 36] Diabetes Panc…”
BackgroundInfluentialHoof, D. V., Mendelsohn, A. D., Seerke, R., Desai, T. A., & German, M. S. (2011) · Stem Cell Research · doi:10.1016/j.scr.2011.02.004 · Cited by 51
Mason, C., & Dunnill, P. (2009) · Regenerative medicine · doi:10.2217/17460751.4.2.153 · Cited by 49
Current status of islet cell transplantation
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“diabetes in experimental model systems with human embryonic stem cell derived cell products represents an unprecedented result that underlies the importance of human embryonic stem cell research to provide a potentially unlimited source of insulin producing cells [143, 144].”
A Stem Cell Approach to Cure Type 1 DiabetesPreprint
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El‐Badri, N., & Ghoneim, M. A. (2013) · Journal of Nucleic Acids · doi:10.1155/2013/194858 · Cited by 43
“Growth factor cocktails designed to induce effective differentiation of ESCs into insulin producing cells have been well-characterized [8].”
BackgroundMethodZhang, Z., Rankin, S. A., & Zorn, A. M. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.02.024 · Cited by 42
“A detailed knowledge of these complex signaling events will facilitate efforts to direct the differentiation of human stem cells into different endoderm lineages (Kroon et al., 2008; Si-Tayeb et al., 2010; Spence et al., 2011; Zaret, 2008).”
BackgroundA small molecule differentiation inducer increases insulin production by pancreatic β cells
Dioum, E., Osborne, J. K., Goetsch, S., Russell, J., Schneider, J., & Cobb, M. (2011) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1118526109 · Cited by 48
Insulin-producing Surrogate β-cells From Embryonic Stem Cells: Are We There Yet?
Naujok, O., Burns, C., Jones, P. M., & Lenzen, S. (2011) · Molecular Therapy · doi:10.1038/mt.2011.165 · Cited by 49
Emerging diabetes therapies: Bringing back the β-cells
Basile, G., Qadir, M. M. F., Mauvais‐Jarvis, F., Vetere, A., Shoba, V. M., Modell, A. E., Pastori, R. L., Russ, H. A., Wagner, B. K., & Domínguez‐Bendala, J. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101477 · Cited by 56
“In contrast, when PE cells were transplanted into immune deficient mice, grafts gave rise to fully functional, glucose-responsive stem cellderived b-like cells (sBCs) that can reverse chemically-induced diabetes [5,6,10,11].”
BackgroundFrom Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges
Ghoneim, M. A., Refaie, A. F., Elbassiouny, B. L., Gabr, M. M., & Zakaria, M. M. (2020) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-10036-3 · Cited by 62
“The device was loaded with pancreatic progenitor cells derived from hESCs [8].”
BackgroundMethodThe bioartificial pancreas (BAP): Biological, chemical and engineering challenges
Iacovacci, V., Ricotti, L., Menciassi, A., & Dario, P. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.08.107 · Cited by 68
Aguayo-Mazzucato, C., DiIenno, A. R., Hollister-Lock, J., Cahill, C., Sharma, A. J., Weir, G., Colton, C., & Bonner-Weir, S. (2015) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2015-2632 · Cited by 47
Advances and challenges in the differentiation of pluripotent stem cells into pancreatic β cells.
Abdelalim, E. M., & Emara, M. (2015) · World Journal of Stem Cells · doi:10.4252/wjsc.v7.i1.174 · Cited by 47
Islet β-Cell-Specific MafA Transcription Requires the 5′-Flanking Conserved Region 3 Control Domain
Raum, J. C., Hunter, C. S., Artner, I., Henderson, E. K., Guo, M., Elghazi, L., Sosa-Pineda, B., Ogihara, T., Mirmira, R., Sussel, L., et al. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01396-09 · Cited by 47
p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
Kondo, T., Khattabi, I. E., Nishimura, W., Laybutt, D., Geraldes, P. M., Shah, S., King, G., Bonner-Weir, S., Weir, G., & Sharma, A. J. (2009) · Molecular Endocrinology · doi:10.1210/me.2008-0482 · Cited by 47
Manaph, N. P. A., Sivanathan, K. N., Nitschke, J., Zhou, X., Coates, P. T. H., & Drogemuller, C. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1396-5 · Cited by 52
“Conclusively, the MSC-based protocols take minimal time (7–25 days) to generate beta cell-like cells in vitro [94, 95].”
Gabr, M. M., Zakaria, M. M., Refaie, A. F., Khater, S. M., Ashamallah, S. A., Ismail, A. M., El‐Badri, N., & Ghoneim, M. A. (2014) · BioMed Research International · doi:10.1155/2014/832736 · Cited by 45
Epigenetics and diabetes treatment: an unrealized promise?
Bramswig, N. C., & Kaestner, K. H. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.02.002 · Cited by 45
“protocols used for the differentiation of embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) towards the β-cell fate [33, 34].”
BackgroundSuppression of Alk8-mediated Bmp signaling cell-autonomously induces pancreatic β-cells in zebrafish
Chung, W.-S., Andersson, O., Row, R. H., Kimelman, D., & Stainier, D. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0910205107 · Cited by 46
“Several bmp genes, including bmp2b, bmp4, and bmp7, are known to be expressed on the ventral side of the gastrula, whereas genes encoding secreted Bmp antagonists, such as Noggin1, Chordin, and Gremlin1a, are expressed on the dorsal side (11, 20).”
ResultHaumaître, C., Lenoir, O., & Scharfmann, R. (2009) · Cell Cycle · doi:10.4161/cc.8.4.7610 · Cited by 46
Liu, H.-S., Li, R.-H., Liao, H.-K., Min, Z., Wang, C., Yu, Y., Shi, L., Dan, J., Hayek, A., Martinez, L. M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23525-x · Cited by 45
Kim, H., Na, D. L., Lee, N. K., Kim, A. R., Lee, S., & Jang, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041272 · Cited by 47
Sex Differences in Maturation of Human Embryonic Stem Cell–Derived β Cells in Mice
Saber, N., Bruin, J. E., O’Dwyer, S. M., Schuster, H., Rezania, A., & Kieffer, T. J. (2018) · Endocrinology · doi:10.1210/en.2018-00048 · Cited by 49
Epigenetic modifications and long noncoding RNAs influence pancreas development and function
Arnes, L., & Sussel, L. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.02.008 · Cited by 54
Alternative splicing: An important mechanism in stem cell biology
Chen, K. (2015) · World Journal of Stem Cells · doi:10.4252/wjsc.v7.i1.1 · Cited by 50
Emerging Medical Devices for Minimally Invasive Cell Therapy
O’Cearbhaill, E. D., Ng, K. S., & Karp, J. M. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2013.10.020 · Cited by 47
Wang, P.-R., McKnight, K. D., Wong, D. J., Rodriguez, R. T., Sugiyama, T., Gu, X.-Y., Ghodasara, A., Qu, K., Chang, H. Y., & Kim, S. K. (2012) · Stem Cells and Development · doi:10.1089/scd.2011.0416 · Cited by 45
“However, exposure of mouse and human ES cells to a combination of purified Wnt and Activin A, which only recapitulates a subset of the signals that regulate endoderm development, is a common method for producing heterogeneous cultures that include progeny with endoderm-like properties [7,12].”
Cell-based treatments for diabetes
Jones, P. M., Courtney, M. L., Burns, C. J., & Persaud, S. J. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.06.014 · Cited by 38
Youngblood, R. L., Sampson, J. P., Lebioda, K. R., Spicer, G., & Shea, L. D. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.06.032 · Cited by 57
Establishment of human pluripotent stem cell-derived pancreatic β-like cells in the mouse pancreas
Ma, H.-T., Wert, K., Shvartsman, D., Melton, D., & Jaenisch, R. (2018) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1702059115 · Cited by 44
Higuchi, A., Kumar, S. S., Ling, Q., Alarfaj, A. A., Munusamy, M. A., Murugan, K., Hsu, S.-T., Benelli, G., & Umezawa, A. (2016) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2016.09.002 · Cited by 57
Generation of Functional Beta-Like Cells from Human Exocrine Pancreas
Lima, M., Muir, K. R., Docherty, H., McGowan, N. W. A., Forbes, S., Heremans, Y., Heimberg, H., Casey, J., & Docherty, K. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156204 · Cited by 44
“progenitors β-cells [5], with the insulin content and functionality of hPC-derived fully differentiated β-like cells [10,11], and with β-like cells generated from human ductal-enriched cells [28].”
BackgroundPellegrini, S., Ungaro, F., Mercalli, A., Melzi, R., Sebastiani, G., Dotta, F., Broccoli, V., Piemonti, L., & Sordi, V. (2015) · Acta Diabetologica · doi:10.1007/s00592-015-0726-z · Cited by 44
“For the differentiation of human iPSCs, we selected as a backbone the most efficient protocol for in vitro differentiation of ESCs [31].”
BackgroundInfluentialDicer1 Is Required to Repress Neuronal Fate During Endocrine Cell Maturation
Kanji, M., Martı́n, M. G., & Bhushan, A. (2013) · Diabetes · doi:10.2337/db12-0841 · Cited by 46
Saito, H., Takeuchi, M., Chida, K., & Miyajima, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028209 · Cited by 44
“Although pancreatic cells derived from ES cells did not form any islet-like structures in vitro, functional islets were formed in kidney capsules of immune-deficient mice several months after the transplantation [9].”
InfluentialThrower, S., & Bingley, P. J. (2011) · British Medical Bulletin · doi:10.1093/bmb/ldr020 · Cited by 26
New perspectives in stem cell research: beyond embryonic stem cells
Leeb, C., Jurga, M., McGuckin, C., Forraz, N., Thallinger, C., Moriggl, R., & Kenner, L. (2011) · Cell Proliferation · doi:10.1111/j.1365-2184.2010.00725.x · Cited by 44
Ren, X., Zhang, J., Gong, X., Niu, X., Zhang, X.-J., Chen, P., & Zhang, X.-J. (2010) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmq046 · Cited by 44
Induced human pluripotent stem cells: promises and open questions
Rolletschek, A., & Wobus, A. M. (2009) · Biological Chemistry · doi:10.1515/bc.2009.103 · Cited by 45
“, 2008) or to develop insulin-producing cells that reverted glycaemia in diabetic animals (Kroon et al., 2008).”
BackgroundChmielowiec, J., Szlachcic, W. J., Yang, D., Scavuzzo, M. A., Wamble, K., Sarrion-Perdigones, A., Sabek, O., Venken, K., & Borowiak, M. (2022) · Nature Communications · doi:10.1038/s41467-022-29646-1 · Cited by 43
Considerations and challenges of islet transplantation and future therapies on the horizon
Walker, S. L. M., Appari, M., & Forbes, S. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00310.2021 · Cited by 47
“8 to scar formation around the site limiting the release of insulin [100].”
BackgroundClinical islet transplantation: Current progress and new frontiers
Marfil‐Garza, B. A., Shapiro, A. M. J., & Kin, T. (2021) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.891 · Cited by 57
Vascularized Organoids: A More Complete Model
Yu, J. S. (2020) · International Journal of Stem Cells · doi:10.15283/ijsc20143 · Cited by 59
“, dipeptidyl peptidase 4) increased drastically after making a joint with blood vessels (23).”
BackgroundArroyave, F., Montaño, D., & Lizcano, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228685 · Cited by 52
“Between 2005 and 2008 Baetge’s group [171,174,175], developed techniques to differentiate hESCs towards β-cells.”
Background(Re)generating Human Beta Cells: Status, Pitfalls, and Perspectives
Baeyens, L., Lemper, M., Staels, W., Groef, S. D., Leu, N. D., Heremans, Y., German, M. S., & Heimberg, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00034.2016 · Cited by 52
Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells
Rostovskaya, M., Bredenkamp, N., & Smith, A. G. (2015) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2014.0365 · Cited by 43
Hoveizi, E., Nabiuni, M., Parivar, K., Ai, J., & Massumi, M. (2014) · Journal of Biomedical Materials Research. Part A · doi:10.1002/jbm.a.35039 · Cited by 43
Adaptive changes of human islets to an obesogenic environment in the mouse
Gargani, S., Thévenet, J., Yuan, J., Lefebvre, B., Delalleau, N., Gmyr, V., Hübert, T., Duhamel, A., Pattou, F. N., & Kerr-Conte, J. A. (2012) · Diabetologia · doi:10.1007/s00125-012-2775-y · Cited by 45
“The transplantation of human islets into immune-compromised mice is a validated technique with which to study human beta cells in an in vivo environment [9] and when human C-peptide levels are measured, this technique provides a quantitative assessment of human islet function [10, 11].”
BackgroundExpression of MafA in pancreatic progenitors is detrimental for pancreatic development
Nishimura, W., Bonner-Weir, S., & Sharma, A. J. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.06.029 · Cited by 43
“Consistent with this suggestion, MafA expression accompanied the acquisition of glucose responsiveness in insulin+ cells differentiated from human ES cells (Kroon et al., 2008).”
BackgroundRegenberg, A., Mathews, D., Blass, D. M., Bok, H., Coyle, J., Duggan, P., Faden, R., Finkel, J., Gearhart, J. D., Hillis, A., et al. (2008) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1038/jcbfm.2008.98 · Cited by 43
“…efforts to regenerate heart muscle (Behfar and Terzic, 2007; Kocher et al, 2007; Boyle et al, 2006), repair vision loss (Limb et al, 2006; Adler, 2008; Vemuganti et al, 2007), and methods for cell-based insulin replacement strategies to treat diabetes (D’Amour et al, 2006; Kroon et al, 2008).”
Dunn, K. K., & Palecek, S. P. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00110 · Cited by 41
“In addition, hESC-derived pancreatic progenitors differentiated into mature insulin-producing β-cells that expressed prohormone convertase enzymes upon implantation below the left kidney of immune-deficient mice (46, 47).”
BackgroundEbrahimi, A., Ahmadi, H., Ghasrodashti, Z. P., Tanide, N., Shahriarirad, R., Erfani, A., Ranjbar, K., & Ashkani‐Esfahani, S. (2021) · Bosnian Journal of Basic Medical Sciences · doi:10.17305/bjbms.2021.5508 · Cited by 44
“Several in vivo and in vitro studies have been conducted to produce IPCs and functional pancreatic islet cells from human ESCs and ASCs [293-297].”
BackgroundInfluentialMukherjee, S., Yadav, G., & Kumar, R. (2021) · World Journal of Stem Cells · doi:10.4252/wjsc.v13.i6.521 · Cited by 48
Wesolowska‐Andersen, A., Jensen, R. R., Perez‐Alcantara, M., Beer, N. L., Duff, C. E., Nylander, V., Gosden, M. E., Witty, L., Bowden, R. J., McCarthy, M. I., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.11.010 · Cited by 49
“When trans- planted into immunocompromised mice, the hPSC- derived PPs are able to give rise to all lineages of the pancreas (Kelly et al., 2011; Kroon et al., 2008; Rezania et al., 2012, 2013), supporting their similarity to multipotent PPs observed during development.”
BackgroundPluripotent Stem Cells: The Last 10 Years
Kimbrel, E. A., & Lanza, R. (2016) · Regenerative Medicine · doi:10.2217/rme-2016-0117 · Cited by 45
Metadata
- Authors
- 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.
- Venue
- Nature Biotechnology
- Published
- 2008-02-20
- Volume
- 26
- Issue
- 4
- Pages
- 443-452
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2106219965
- Cited by
- 1,843
- References
- 0
- Citations by year
- 2026: 26 · 2025: 44 · 2024: 46 · 2023: 88 · 2022: 67 · 2021: 81 · 2020: 85 · 2019: 76 · 2018: 87 · 2017: 98 · 2016: 122 · 2015: 116 · 2014: 156 · 2013: 168 · 2012: 154
- FWCI
- 150.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- human embryonic stem cells, beta cell differentiation, glucose-dependent insulin secretion, islet transplantation, diabetes cell therapy, C-peptide, proinsulin processing, streptozotocin-induced hyperglycemia
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Endoderm, Glucose, Humans, Insulin, Cell Culture Techniques, Pancreas, Artificial, Tissue Engineering, Cell Proliferation, Insulin-Secreting Cells, Mice, Embryonic Stem Cells
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