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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
Flagged first, then by citations
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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BackgroundFernandez, A., Huggins, I. J., Perna, L., Brafman, D. A., Lu, D.-S., Yao, S., Gaasterland, T., Carson, D., & Willert, K. (2014) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1323697111 · Cited by 110
Regenerative Medicine as Applied to General Surgery
Orlando, G., Wood, K. J., Coppi, P. D., Baptista, P. M., Binder, K. W., Bitar, K. N., Breuer, C. K., Burnett, L., Christ, G. J., Farney, A. C., et al. (2012) · Annals of Surgery · doi:10.1097/sla.0b013e318243a4db · Cited by 113
Phadnis, S., Joglekar, M., Dalvi, M., Muthyala, S., Nair, P., Ghaskadbi, S., Bhonde, R., & Hardikar, A. (2011) · Cytotherapy · doi:10.3109/14653249.2010.523108 · Cited by 110
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Volarevic, V., Ljujić, B., Stojkovic, P., Lukić, A., Arsenijević, N., & Stojkovic, M. (2011) · British Medical Bulletin · doi:10.1093/bmb/ldr027 · Cited by 109
Derivation of insulin-producing cells from human embryonic stem cells.
van Hoof, D., D'Amour, K., & German, M. (2009) · Stem Cell Research · doi:10.1016/j.scr.2009.08.003 · Cited by 108
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Guo, T., & Hebrok, M. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0004 · Cited by 106
Han, X., Chen, H., Huang, D., Chen, H., Fei, L., Cheng, C., Huang, H., Yuan, G., & Guo, G. (2018) · Genome biology · doi:10.1186/s13059-018-1426-0 · Cited by 122
Gabr, M. M., Zakaria, M. M., Refaie, A. F., Ismail, A. M., Abou-El-Mahasen, M. A., Ashamallah, S. A., Khater, S. M., El-Halawani, S. M., Ibrahim, R. Y., Uin, G. S., et al. (2013) · Cell Transplantation · doi:10.3727/096368912x647162 · Cited by 116
“Human embryonic stem cells (h-ESCs) can be expanded in the undifferentiated state and differentiated to all cell types including insulin-producing cells (IPCs) (22,24,36).”
BackgroundSulzbacher, S., Schroeder, I., Truong, T., & Wobus, A. (2009) · Stem Cell Reviews and Reports · doi:10.1007/s12015-009-9061-5 · Cited by 107
“In most of the recent studies, consequently, for the differentiation of ES cells into definitive endoderm, high concentrations of activin A (100 ng/ml) were used [7, 8, 24, 58, 60, 64, 67, 68].”
BackgroundMethodInfluentialHuman embryonic and induced pluripotent stem cells in clinical trials.
Ilic, D., Devito, L., Miere, C., & Codognotto, S. (2015) · British Medical Bulletin · doi:10.1093/bmb/ldv045 · Cited by 106
“These cells, when implanted into mice, reacted to glucose stimulation; human insulin and C-peptide were detected in sera at levels similar to those of mice transplanted with approximately 3000 human islets.(18) Using surface markers, they were able to separate pancreatic hormone-expressing endocrine cells into differe…”
ResultWierup, N., Sundler, F., & Heller, R. S. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0122 · Cited by 128
“The same group also showed, when aiming at producing endocrine cells from human embryonic stem cells, that ghrelin cells appear as a separate cell type distinct from a-, b-, d- and PP-cells after certain procedures (D’Amour et al. 2006, Kroon et al. 2008).”
New perspectives in human stem cell therapeutic research
Trounson, A. (2009) · BMC Medicine · doi:10.1186/1741-7015-7-29 · Cited by 106
“ESCs, and potentially iPSCs, can be directed into a wide range of cell types and proof of concept studies are taking place for preclinical studies to correct human diseases in animal models of a variety of conditions, including diabetes [27], myocardial infarction [28], Parkinson's disease [29], and liver disease [30].”
BackgroundBi, H., Ye, K., & Jin, S. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2019.119673 · Cited by 105
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BackgroundCurrent Status of Islet Cell Replacement and Regeneration Therapy
Halban, P. A., German, M. S., Kahn, S. E., & Weir, G. C. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1819 · Cited by 90
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BackgroundAghazadeh, Y., Poon, F., Sarangi, F., Wong, F., Khan, S. T., Sun, X., Hatkar, R., Cox, B., Nunes, S. S., & Nostro, M. C. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.08.001 · Cited by 124
Kim, J., Shim, I. K., Hwang, D. G., Lee, Y. N., Kim, M., Kim, H., Kim, S.-W., Lee, S., Kim, S. C., Cho, D., et al. (2019) · Journal of Materials Chemistry B · doi:10.1039/c8tb02787k · Cited by 141
Toyoda, T., Mae, S.-I., Tanaka, H., Kondo, Y., Funato, M., Hosokawa, Y., Sudo, T., Kawaguchi, Y., & Osafune, K. (2015) · Stem Cell Research · doi:10.1016/j.scr.2015.01.007 · Cited by 103
Thatava, T., Kudva, Y. C., Edukulla, R., Squillace, K. A., Lamo, J. G. D., Khan, Y. K., Sakuma, T., Ohmine, S., Terzic, A., & Ikeda, Y. (2012) · Molecular Therapy · doi:10.1038/mt.2012.245 · Cited by 98
Carmen, J., Burger, S. R., McCaman, M. T., & Rowley, J. A. (2011) · Regenerative Medicine · doi:10.2217/rme.11.105 · Cited by 102
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BackgroundMethodResultInfluentialSelf-citationGeneration of beta cells from human pluripotent stem cells: Potential for regenerative medicine
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BackgroundMicropatterning of human embryonic stem cells dissects the mesoderm and endoderm lineages.
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MethodTuch, B. E., & Kannangara, K. (2008) · Drug Discovery Today Therapeutic Strategies · doi:10.1016/j.ddstr.2009.05.002 · Cited by 1
van der Meulen, T., Xie, R., Kelly, O. G., Vale, W., Sander, M., & Huising, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052181 · Cited by 98
“1 expression in the process) as well as beta cells following engraftment in vivo [10,11], it is possible that some of these Ucn 3 insulin- negative cells are in fact hESC-derived Ucn 3 alpha cells.”
InfluentialSelf-citationSong, H., Yoon, C., Kattman, S. J., Dengler, J., Massé, S., Thavaratnam, T., Gewarges, M., Nanthakumar, K., Rubart, M., Keller, G., et al. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0905729106 · Cited by 98
“Additionally, it now appears possible to identify and isolate specific ESC-derived cardiac progenitors (ESCCPs) (9–11), opening the possibility of using progenitor cells for cardiac cell therapy, as has been explored using pancreatic endoderm progenitors for the generation of insulin responsive islet-like cells (12, 1…”
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“Earlier reports demonstrated that, upon transplantation into rodents, a portion of these cells will spontaneously differentiate into b-like cells through an unknown mechanism (17,19), a phenomenon that is the basis for a clinical trial being conducted by ViaCyte, Inc.”
BackgroundPettinato, G., Wen, X., & Zhang, N. (2014) · Scientific Reports · doi:10.1038/srep07402 · Cited by 97
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Peiris, H. S., Bonder, C. S., Coates, P. T., Keating, D. J., & Jessup, C. F. (2013) · Diabetes · doi:10.2337/db13-0617 · Cited by 105
Morphogenetics of early thyroid development
Fagman, H., & Nilsson, M. (2010) · Journal of Molecular Endocrinology · doi:10.1677/jme-10-0084 · Cited by 90
“2006, Kroon et al .”
Pepper, A. R., Pawlick, R., Bruni, A., Wink, J., Rafiei, Y., O’Gorman, D., Yan-Do, R., Gala-Lopez, B., Kin, T., MacDonald, P. E., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.05.004 · Cited by 96
Kirk, K., Hao, E., Lahmy, R., & Itkin-Ansari, P. (2014) · Stem Cell Research · doi:10.1016/j.scr.2014.03.003 · Cited by 96
“Recently multi-step protocols were developed and optimized to differentiate the CyT49 hESC line from the naïve state through key stages of pancreatic development (D'Amour et al., 2006; Kroon et al., 2008; Kelly et al., 2011; Schulz et al., 2012); definitive endoderm, foregut, and pancreatic epithelium, that efficientl…”
BackgroundMethodInfluentialPetersen, M., Azad, A., Ingvorsen, C., Hess, K., Hansson, M., Grapin-Botton, A., & Honoré, C. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.08.009 · Cited by 96
“…in both mouse (Nelson et al., 2007; Schaffer et al., 2013; Taylor et al., 2013) and hESC-derived pancreatic cell populations (Kelly et al., 2011; Kroon et al., 2008; Rezania et al., 2013; Russ et al., 2015) have led to the assumption that mature b cells derive from endocrine progenitors born…”
BackgroundRat islet cell aggregates are superior to islets for transplantation in microcapsules
O'Sullivan, E., Johnson, A., Omer, A., Hollister-Lock, J., Bonner-Weir, S., Colton, C. K., & Weir, G. (2010) · Diabetologia · doi:10.1007/s00125-009-1653-8 · Cited by 96
“There has been impressive recent progress in finding a new source of sufficient numbers of healthy beta cells, with attractive potential sources being embryonic stem cells, induced pluripotent cells and porcine islet cells [4, 5 ]. However, their immunogenicity will likely remain an obstacle, hence the importance of i…”
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“Months after transplantation in vivo, ES cell-derived beta cells were able to advance or complete their differentiation, further mature, and become glucose responsive, as evidenced by the successful treatment of pre-existing diabetes in immune-deficient mice following transplantation [13, 14].”
BackgroundInfluentialLatres, E., Finan, D. A., Greenstein, J. L., Kowalski, A. J., & Kieffer, T. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.007 · Cited by 124
Oh, K., Kim, S. R., Kim, D., Seo, M. W., Lee, C., Lee, H. M., Oh, J.-E., Choi, E. Y., Lee, D., Gho, Y. S., et al. (2015) · ACS Nano · doi:10.1021/acsnano.5b02997 · Cited by 100
Vascular instruction of pancreas development
Cleaver, O. B., & Dor, Y. (2012) · Development · doi:10.1242/dev.065953 · Cited by 99
“Interestingly, it has been reported that ES cell-derived pancreatic progenitor cells most efficiently mature into -cells when grafted to mice (Kroon et al., 2008).”
The endocrine pancreas: insights into development, differentiation, and diabetes
Mastracci, T. L., & Sussel, L. (2012) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.44 · Cited by 100
iPSC-derived β cells model diabetes due to glucokinase deficiency.
Hua, H.-Q., Shang, L.-S., Martinez, H., Freeby, M., Gallagher, M., Ludwig, T., Deng, L.-Y., Greenberg, E., Leduc, C., Chung, W., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67638 · Cited by 93
“Human pluripotent stem cells, including iPSCs and human ES cells, have the capacity to differentiate into insulin-producing cells (2), which display key properties of true β cells, including glucose-stimulated insulin secretion upon maturation in vivo (3).”
RetractedHu, X., Gattis, C., Olroyd, A. G., Friera, A. M., White, K. A., Young, C., Basco, R., Lamba, M., Wells, F., Ankala, R., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adg5794 · Cited by 104
RFX6 Regulates Insulin Secretion by Modulating Ca2+ Homeostasis in Human β Cells
Chandra, V., Albagli, O., Hastoy, B., Piccand, J., Randriamampita, C., Vaillant, E., Cavé, H., Busiah, K., Froguel, P., Vaxillaire, M., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.11.010 · Cited by 94
“Surprisingly, the level of RFX6 expression is rarely measured in protocols aiming at generating functional b cells from human embryonic stem cells (hESCs) (Kroon et al., 2008; Rezania et al., 2012).”
BackgroundConformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes
Stock, A. A., Manzoli, V., Toni, T. D., Abreu, M. M., Poh, Y., Ye, L., Roose, A. N., Pagliuca, F., Thanos, C., Ricordi, C., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.11.004 · Cited by 90
“In contrast to previous stem cell-derived insulin-secreting cell products requiring further differentiation in vivo after transplantation (Kroon et al., 2008), these SC islets are terminally differentiated at the time of transplantation and have shown efficacy in diabetes reversal in vivo in rodent models (Pagliuca et…”
BackgroundResultKim, Y., Kim, H., Ko, U. H., Oh, Y., Lim, A., Sohn, J., Shin, J. H., Kim, H., & Han, Y. (2016) · Scientific Reports · doi:10.1038/srep35145 · Cited by 101
From In Vitro to In Situ Tissue Engineering
Sengupta, D., Waldman, S. D., & Li, S. (2014) · Annals of Biomedical Engineering · doi:10.1007/s10439-014-1022-8 · Cited by 102
Concise review: Clinical programs of stem cell therapies for liver and pancreas
Lanzoni, G., Oikawa, T., Wang, Y., Cui, C.-B., Carpino, G., Cardinale, V., Gerber, D. A., Gabriel, M., Domínguez‐Bendala, J., Furth, M. E., et al. (2013) · Stem Cells · doi:10.1002/stem.1457 · Cited by 100
“Human ES cells can mature into -like islet cells, but they are not the same as normal ones [119].”
InfluentialThe use of stem cells for pancreatic regeneration in diabetes mellitus
Bouwens, L., Houbracken, I., & Mfopou, J. K. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.145 · Cited by 92
New advances in type 1 diabetes
Subramanian, S., Khan, F. N., & Hirsch, I. B. (2024) · BMJ · doi:10.1136/bmj-2023-075681 · Cited by 105
Song, W., Lu, Y., Frankel, A. S., An, D., Schwartz, R. E., & Ma, M. (2015) · Scientific Reports · doi:10.1038/srep16884 · Cited by 91
Reprogramming of human pancreatic exocrine cells to β-like cells
Lemper, M., Leuckx, G., Heremans, Y., German, M. S., Heimberg, H., Bouwens, L., & Baeyens, L. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.193 · Cited by 89
Lu, H., Narayanan, K., Lim, S.-X., Gao, S., Leong, M. F., & Wan, A. C. A. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.11.077 · Cited by 95
Ohmine, S., Squillace, K. A., Hartjes, K. A., Deeds, M. C., Armstrong, A. S., Thatava, T., Sakuma, T., Terzic, A., Kudva, Y. C., & Ikeda, Y. (2012) · Aging · doi:10.18632/aging.100428 · Cited by 89
“In preclinical studies, human ES cells have been differentiated into insulin-producing cells [3-5], which can reverse the course of diabetes [3].”
BackgroundROCKII inhibition promotes the maturation of human pancreatic beta-like cells
Ghazizadeh, Z., Kao, D.-I., Amin, S., Cook, B. D., Rao, S. D., Zhou, T., Zhang, T., Xiang, Z.-Y., Kenyon, R., Kaymakcalan, O. E., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00129-y · Cited by 88
Szot, G. L., Yadav, M., Lang, J., KROON, E. J., Kerr, J. M., Kadoya, K., Brandon, E. P., Baetge, E. E., Bour-Jordan, H., & Bluestone, J. A. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.12.001 · Cited by 92
Self-citationGodfrey, K. J., Mathew, B., Bulman, J. C., Shah, O., Clément, S., & Gallicano, G. I. (2011) · Diabetic Medicine · doi:10.1111/j.1464-5491.2011.03433.x · Cited by 97
Stem Cell Platforms for Regenerative Medicine
Nelson, T. J., Behfar, A., Yamada, S., Martinez-Fernandez, A., & Terzic, A. (2009) · Clinical and Translational Science · doi:10.1111/j.1752-8062.2009.00096.x · Cited by 88
Raptor regulates functional maturation of murine beta cells
Ni, Q., Gu, Y., Xie, Y., Yin, Q., Zhang, H., Nie, A., Li, W., Wang, Y., Ning, G., Wang, W., et al. (2017) · Nature Communications · doi:10.1038/ncomms15755 · Cited by 94
A human beta cell line with drug inducible excision of immortalizing transgenes
Benazra, M., Lecomte, M., Colace, C., Müller, A., Machado, C., Pechberty, S., Bricout-Neveu, E., Grenier-Godard, M., Solimena, M., Scharfmann, R., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.09.008 · Cited by 87
“Since the important original contribution of the Viacyte group to generate endocrine cells from hESCs [4,5], recent advances have been made in this field to obtain in vitro more fully mature pancreatic endocrine cells [6,7].”
BackgroundPancreas development in humans
Pan, F. C., & Brissova, M. (2014) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000047 · Cited by 87
Kudva, Y. C., Ohmine, S., Greder, L. V., Dutton, J. R., Armstrong, A. S., Lamo, J. G. D., Khan, Y. K., Thatava, T., Hasegawa, M., Fusaki, N., et al. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2011-0044 · Cited by 87
Notch signaling as gatekeeper of rat acinar-to-beta-cell conversion in vitro.
Baeyens, L., Bonné, S., Bos, T., Rooman, I., Peleman, C., Lahoutte, T., German, M., Heimberg, H., & Bouwens, L. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.01.047 · Cited by 87
Song, S., & Roy, S. (2015) · Biotechnology and Bioengineering · doi:10.1002/bit.25895 · Cited by 103
“In 2014, ViaCyte launched a Phase I/II clinical trial using a pouch approach with human embryonic stem cell-derived, encapsulated cell replacement therapy (Agulnick et al., 2015; Kroon et al., 2008).”
BackgroundInfluentialThe safety of human pluripotent stem cells in clinical treatment
Simonson, O. E., Domogatskaya, A., Volchkov, P., & Rodin, S. (2015) · Annals of Medicine · doi:10.3109/07853890.2015.1051579 · Cited by 91
Jin, S., Yao, H., Weber, J. L., Melkoumian, Z., & Ye, K.-M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050880 · Cited by 86
“The differentiation of DE lineage is the first and also the most critical step in hESC pancreatic differentiation [36,37,38].”
BackgroundMicallef, S. J., Li, X., Schiesser, J. V., Hirst, C. E., Yu, Q. C., Lim, S. M., Nostro, M. C., Elliott, D. A., Sarangi, F., Harrison, L. C., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2379-y · Cited by 136
“[2] and Jiang et al.”
Mao, G.-H., Chen, G.-A., Bai, H.-Y., Song, T.-R., & Wang, Y.-X. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2008.12.030 · Cited by 86
“The same group more recently transferred the differentiated cells at stage 4, which was probably similar to 6th–9th week fetal pancreatic tissues without response to glucose, into mice for further development in vivo, and they found the grafted mice had pancreatic islet function against streptozotocin-induced hypergly…”
MUC1* Mediates the Growth of Human Pluripotent Stem Cells
Hikita, S. T., Kosik, K., Clegg, D., & Bamdad, C. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003312 · Cited by 85
Disallowed and Allowed Gene Expression: Two Faces of Mature Islet Beta Cells
Lemaire, K., Thorrez, L., & Schuit, F. C. (2016) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071715-050808 · Cited by 86
Rare somatic cells from human breast tissue exhibit extensive lineage plasticity
Roy, S., Gascard, P. D., Dumont, N., Zhao, J., Pan, D., Petrie, S. E., Margeta, M., & Tlsty, T. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218682110 · Cited by 87
Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium
Magenheim, J., Klein, A. M., Stanger, B., Ashery-Padan, R., Sosa-Pineda, B., Gu, G.-Q., & Dor, Y. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.08.006 · Cited by 84
“Recent progress in this area allows the efficient derivation of ESC-derived Pdx1 pancreatic epithelial cells (Borowiak et al., 2009; Chen et al., 2009; D'Amour et al., 2005, 2006; Kroon et al., 2008).”
BackgroundBorowiak, M., & Melton, D. A. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.08.006 · Cited by 74
Narayanan, K., Lim, V. Y., Shen, J., Tan, Z. W., Rajendran, D., Luo, S.-C., Gao, S., Wan, A. C. A., & Ying, J. Y. (2014) · Tissue Engineering Part A · doi:10.1089/ten.tea.2013.0257 · Cited by 83
“Intraperitoneal GTT results were similar to the previously reported results.(19,20) It was noted that teratomas formed after week 10 in the diabetic animals implanted with differentiated cells, indicating the presence of residual pluripotent cells.”
In vivo chemical reprogramming of astrocytes into neurons
Ma, Y., Xie, H., Du, X., Wang, L., Jin, X., Zhang, Q., Han, Y., Sun, S., Wang, L., Li, X., et al. (2021) · Cell Discovery · doi:10.1038/s41421-021-00243-8 · Cited by 108
Diabetes mellitus: new challenges and innovative therapies
Sena, C. M., Bento, C. F., Pereira, P., & Seiça, R. M. F. (2010) · The EPMA Journal · doi:10.1007/s13167-010-0010-9 · Cited by 92
Generating human antral and fundic gastric organoids from pluripotent stem cells
Broda, T. R., McCracken, K., & Wells, J. M. (2018) · Nature Protocols · doi:10.1038/s41596-018-0080-z · Cited by 81
Encapsulated Islet Transplantation: Where Do We Stand?
Vaithilingam, V., Bal, S., & Tuch, B. E. (2017) · The Review of Diabetic Studies · doi:10.1900/rds.2017.14.51 · Cited by 96
“ViaCyte LLC (San Diego, CA), a pioneer in hESC differentiation to pancreatic lineages, demonstrated the feasibility of encapsulating pancreatic progenitors into a macrodevice (TheraCyte) that mature into glucose-responsive insulinproducing cells and other endocrine cells upon transplantation into mice [209, 210].”
BackgroundMaking surrogate β-cells from mesenchymal stromal cells: Perspectives and future endeavors
Bhonde, R. R., Sheshadri, P., Sharma, S., & Kumar, A. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.11.006 · Cited by 76
Immune Tolerance for Autoimmune Disease and Cell Transplantation
Luo, X., Miller, S. D., & Shea, L. D. (2016) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-110315-020137 · Cited by 91
“Transplantation of allogeneic cells from deceased donors is a promising option (5, 6), but universal stem cell banks provide a potentially unlimited source of progenitor cells and have significant economic advantages relative to autologous sources (7, 8).”
BackgroundAn, D., Ji, Y.-W., Chiu, A., Lu, Y.-C., Song, W., Zhai, L., Qi, L., Luo, D., & Ma, M.-L. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2014.10.032 · Cited by 80
β-Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells
Sui, L., Danzl, N., Campbell, S. R., Viola, R., Williams, D. J., Xing, Y., Wang, Y., Phillips, N., Poffenberger, G., Johannesson, B., et al. (2017) · Diabetes · doi:10.2337/db17-0120 · Cited by 79
“1018-NT-b-Cell Clusters Maintain Normal Blood Glucose Level in Mice With STZ-Induced Diabetes To determine whether maturation to fully mature b-cells occurred in vivo, we transplanted 1018-NT-b-cell clusters containing 1–2 million cells subcutaneously into immunodeficient mice (n = 22) (14,15).”
MethodEconomic 3D-printing approach for transplantation of human stem cell-derived β -like cells
Song, J., & Millman, J. R. (2016) · Biofabrication · doi:10.1088/1758-5090/9/1/015002 · Cited by 89
“Other transplantation sites used in research, such as the kidney capsule [7, 8, 11] or fat pad [12], are not viable for clinical transplantation.”
BackgroundNagaya, M., Katsuta, H., Kaneto, H., Bonner-Weir, S., & Weir, G. (2009) · Journal of Endocrinology · doi:10.1677/joe-08-0482 · Cited by 79
“Promising strategies include differentiation of embryonic stem cells (Kroon et al. 2008), conversion of either pancreatic adult stem/progenitor cells (Bonner-Weir et al. 2000), expansion of existing b-cells (Gershengorn et al. 2004), and xenotransplantation (Cardona et al. 2006, Hering et al. 2006).”
Endodermal differentiation of human pluripotent stem cells to insulin-producing cells in 3D culture
Takeuchi, H., Nakatsuji, N., & Suemori, H. (2014) · Scientific Reports · doi:10.1038/srep04488 · Cited by 87
Jiang, W., Sui, X. Y., Zhang, D., Liu, M., Ding, M., Shi, Y., & Deng, H. (2011) · Stem Cells · doi:10.1002/stem.608 · Cited by 78
Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation
Mora-Castilla, S., Tejedo, J. R., Hmadcha, A., Cahuana, G. M., Martı́n, F., Soria, B., & Bedoya, F. J. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2009.204 · Cited by 70
Three-Dimensional Differentiation of Embryonic Stem Cells into Islet-like Insulin-Producing Clusters
Wang, X.-L., & Ye, K.-M. (2009) · Tissue Engineering. Part A · doi:10.1089/ten.tea.2008.0181 · Cited by 78
Resetting transcription factor control circuitry toward ground-state pluripotency in human
Takashima, Y., Guo, G., Loos, R., Nichols, J., Ficz, G., Krueger, F., Oxley, D., Santos, F., Clarke, J., Mansfield, W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.052 · Cited by 78
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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