Beta Cell Generation by Stem Cell-Derived Implants in Diabetes

Deliverables

Demonstrators, pilots, prototypes (3)

Production of biodegradable microparticles for local release of VEGF, NGF and exenatide

In vitro kinetics and in vivo compatibility should be determined in mice

Human beta cell preparations with QC data for comparative assessment of human iPS-derived implants in preclinical model and their use in screening assay

To be delivered to WP6-9 for interpretation outcome human iPS-derived implants, and to WP6 for screening assay

Human beta cell grafts with QC data for start transplants in subgroup of type 1 diabetes recipients of VCTM implant

To be delivered to WP4 for treatment of patient cohort that ended VCTM-01 trial under immune therapy

Other (2)

Communication network operational

See 3.2 and 3.3 Part B

Time-table for public information on program

See milestone

Publications

Peer reviewed articles (46)

Functional Beta Cell Mass from Device-Encapsulated hESC-Derived Pancreatic Endoderm Achieving Metabolic Control

Author(s): Thomas Robert, Ines De Mesmaeker, Geert M. Stangé, Krista G. Suenens, Zhidong Ling, Evert J. Kroon, Daniel G. Pipeleers
Published in: Stem Cell Reports, Issue 10/3, 2018, Page(s) 739-750, ISSN 2213-6711
DOI: 10.1016/j.stemcr.2018.01.040

The potential and challenges of alternative sources of β cells for the cure of type 1 diabetes

Author(s): Monia Cito, Silvia Pellegrini, Lorenzo Piemonti, Valeria Sordi
Published in: Endocrine Connections, Issue 7/3, 2018, Page(s) R114-R125, ISSN 2049-3614
DOI: 10.1530/EC-18-0012

Plasma GAD65, a Marker for Early β-Cell Loss After Intraportal Islet Cell Transplantation in Diabetic Patients

Author(s): Zhidong Ling, Pieter De Pauw, Daniel Jacobs-Tulleneers-Thevissen, Rui Mao, Pieter Gillard, Christiane S. Hampe, Geert A. Martens, Peter In't Veld, Åke Lernmark, Bart Keymeulen, Frans Gorus, Daniel Pipeleers
Published in: The Journal of Clinical Endocrinology & Metabolism, Issue 100/6, 2015, Page(s) 2314-2321, ISSN 0021-972X
DOI: 10.1210/jc.2015-1216

Combined Analysis of GAD65, miR-375, and Unmethylated Insulin DNA Following Islet Transplantation in Patients With T1D

Author(s): Sarah Roels, Olivier R Costa, Sarah A Tersey, Geert Stangé, Dieter De Smet, Eric V Balti, Pieter Gillard, Bart Keymeulen, Zhidong Ling, Daniel G Pipeleers, Frans K Gorus, Raghavendra G Mirmira, Geert A Martens
Published in: The Journal of Clinical Endocrinology & Metabolism, Issue 104/2, 2018, Page(s) 451-460, ISSN 0021-972X
DOI: 10.1210/jc.2017-02520

Concise Review: Markers for Assessing Human Stem Cell-Derived Implants as β-Cell Replacement in Type 1 Diabetes

Author(s): Daniel Pipeleers, Thomas Robert, Ines De Mesmaeker, Zhidong Ling
Published in: STEM CELLS Translational Medicine, Issue 5/10, 2016, Page(s) 1338-1344, ISSN 2157-6564
DOI: 10.5966/sctm.2015-0187

SLC30A8 polymorphism and BMI complement HLA-A*24 as risk factors for poor graft function in islet allograft recipients

Author(s): Else M. Balke, Simke Demeester, DaHae Lee, Pieter Gillard, Robert Hilbrands, Ursule Van de Velde, Bart J. Van der Auwera, Zhidong Ling, Bart O. Roep, Daniël G. Pipeleers, Bart Keymeulen, Frans K. Gorus
Published in: Diabetologia, Issue 61/7, 2018, Page(s) 1623-1632, ISSN 0012-186X
DOI: 10.1007/s00125-018-4609-z

Differentiation of Sendai Virus-Reprogrammed iPSC into β Cells, Compared with Human Pancreatic Islets and Immortalized β Cell Line

Author(s): Silvia Pellegrini, Fabio Manenti, Raniero Chimienti, Rita Nano, Linda Ottoboni, Francesca Ruffini, Gianvito Martino, Philippe Ravassard, Lorenzo Piemonti, Valeria Sordi
Published in: Cell Transplantation, Issue 27/10, 2018, Page(s) 1548-1560, ISSN 0963-6897
DOI: 10.1177/0963689718798564

Accelerated Progression to Type 1 Diabetes in the Presence of HLA-A*24 and -B*18 Is Restricted to Multiple Islet Autoantibody–Positive Individuals With Distinct HLA-DQ and Autoantibody Risk Profiles

Author(s): Else M. Balke, Eric V. Balti, Bart Van der Auwera, Ilse Weets, Olivier Costa, Simke Demeester, Pascale Abrams, Kristina Casteels, Marina Coeckelberghs, Sylvie Tenoutasse, Bart Keymeulen, Daniel G. Pipeleers, Frans K. Gorus
Published in: Diabetes Care, Issue 41/5, 2018, Page(s) 1076-1083, ISSN 0149-5992
DOI: 10.2337/dc17-2462

Increase Functional β-Cell Mass in Subcutaneous Alginate Capsules With Porcine Prenatal Islet Cells but Loss With Human Adult Islet Cells

Author(s): Ines De Mesmaeker, Thomas Robert, Krista G. Suenens, Geert M. Stangé, Freya Van Hulle, Zhidong Ling, Peter Tomme, Daniel Jacobs-Tulleneers-Thevissen, Bart Keymeulen, Daniel G. Pipeleers
Published in: Diabetes, Issue 67/12, 2018, Page(s) 2640-2649, ISSN 0012-1797
DOI: 10.2337/db18-0709

Human induced pluripotent stem cells differentiate into insulin-producing cells able to engraft in vivo

Author(s): Silvia Pellegrini, Federica Ungaro, Alessia Mercalli, Raffaella Melzi, Guido Sebastiani, Francesco Dotta, Vania Broccoli, Lorenzo Piemonti, Valeria Sordi
Published in: Acta Diabetologica, Issue 52/6, 2015, Page(s) 1025-1035, ISSN 0940-5429
DOI: 10.1007/s00592-015-0726-z

Glucocorticoids and checkpoint tyrosine kinase inhibitors stimulate rat pancreatic beta cell proliferation differentially

Author(s): Sarah Akbib, Jordy Stichelmans, Geert Stangé, Zhidong Ling, Zerihun Assefa, Karine H. Hellemans
Published in: PLOS ONE, Issue 14/2, 2019, Page(s) e0212210, ISSN 1932-6203
DOI: 10.1371/journal.pone.0212210

An analytical comparison of three immunoassay platforms for subpicomolar detection of protein biomarker GAD65

Author(s): Olivier R. Costa, Katrijn Verhaeghen, Sarah Roels, Geert Stangé, Zhidong Ling, Daniel Pipeleers, Frans K. Gorus, Geert A. Martens
Published in: PLOS ONE, Issue 13/3, 2018, Page(s) e0193670, ISSN 1932-6203
DOI: 10.1371/journal.pone.0193670

Pluripotent stem cell replacement approaches to treat type 1 diabetes

Author(s): Silvia Pellegrini, Lorenzo Piemonti, Valeria Sordi
Published in: Current Opinion in Pharmacology, Issue 43, 2018, Page(s) 20-26, ISSN 1471-4892
DOI: 10.1016/j.coph.2018.07.007

The state of the art of islet transplantation and cell therapy in type 1 diabetes

Author(s): Silvia Pellegrini, Elisa Cantarelli, Valeria Sordi, Rita Nano, Lorenzo Piemonti
Published in: Acta Diabetologica, Issue 53/5, 2016, Page(s) 683-691, ISSN 0940-5429
DOI: 10.1007/s00592-016-0847-z

Insights into Islet Differentiation and Maturation through Proteomic Characterization of a Human iPSC-Derived Pancreatic Endocrine Model

Author(s): Corinne Haller, Prasad Chaskar, Julie Piccand, Ornella Cominetti, Charlotte Macron, Loïc Dayon, Marine R-C Kraus
Published in: PROTEOMICS - Clinical Applications, Issue 12/5, 2018, Page(s) 1600173, ISSN 1862-8346
DOI: 10.1002/prca.201600173

Diabetes‐free survival after extended distal pancreatectomy and islet auto transplantation for benign or borderline/malignant lesions of the pancreas

Author(s): Gianpaolo Balzano, Paola Maffi, Rita Nano, Alessia Mercalli, Raffaella Melzi, Francesca Aleotti, Francesco De Cobelli, Paola Magistretti, Marina Scavini, Antonio Secchi, Massimo Falconi, Lorenzo Piemonti
Published in: American Journal of Transplantation, Issue 19/3, 2018, Page(s) 920-928, ISSN 1600-6135
DOI: 10.1111/ajt.15219

Biofabrication of a vascularized islet organ for type 1 diabetes

Author(s): Antonio Citro, Philipp T. Moser, Erica Dugnani, Taufiek K. Rajab, Xi Ren, Daniele Evangelista-Leite, Jonathan M. Charest, Andrea Peloso, Bruno K. Podesser, Fabio Manenti, Silvia Pellegrini, Lorenzo Piemonti, Harald C. Ott
Published in: Biomaterials, Issue 199, 2019, Page(s) 40-51, ISSN 0142-9612
DOI: 10.1016/j.biomaterials.2019.01.035

CCL 2/ MCP ‐1 and CXCL 12/ SDF ‐1 blockade by L‐aptamers improve pancreatic islet engraftment and survival in mouse

Author(s): Antonio Citro, Silvia Pellegrini, Erica Dugnani, Dirk Eulberg, Sven Klussmann, Lorenzo Piemonti
Published in: American Journal of Transplantation, Issue 19/11, 2019, Page(s) 3131-3138, ISSN 1600-6135
DOI: 10.1111/ajt.15518

Islets for Research: Nothing Is Perfect, but We Can Do Better

Author(s): Rita Nano, Julie A. Kerr-Conte, Domenico Bosco, Marie Karlsson, Vanessa Lavallard, Raffaella Melzi, Valery Gmyr, Alessia Mercalli, Thierry Berney, François Pattou, Olle Korsgren, Lorenzo Piemonti
Published in: Diabetes, Issue 68/8, 2019, Page(s) 1541-1543, ISSN 0012-1797
DOI: 10.2337/db19-0367

Selective local irradiation improves islet engraftment and survival in intra–bone marrow islet transplantation

Author(s): Silvia Pellegrini, Elisa Cantarelli, Antonio Citro, Elena Incerti, Lorenzo Piemonti, Valeria Sordi
Published in: Cytotherapy, Issue 21/10, 2019, Page(s) 1025-1032, ISSN 1465-3249
DOI: 10.1016/j.jcyt.2019.07.005

Pharmacological Targeting of GLUT1 to Control Autoreactive T Cell Responses

Author(s): Carla Di Dedda, Debora Vignali, Lorenzo Piemonti, Paolo Monti
Published in: International Journal of Molecular Sciences, Issue 20/19, 2019, Page(s) 4962, ISSN 1422-0067
DOI: 10.3390/ijms20194962

Cell Mass Increase Associated with Formation of Glucose‐Controlling β‐Cell Mass in Device‐Encapsulated Implants of hiPS‐Derived Pancreatic Endoderm

Author(s): Thomas Robert, Ines De Mesmaeker, Freya O. Van Hulle, Krista G. Suenens, Geert M. Stangé, Zhidong Ling, Corinne Haller, Nicolas Bouche, Bart Keymeulen, Marine R.C. Kraus, Daniel G. Pipeleers
Published in: STEM CELLS Translational Medicine, Issue 8/12, 2019, Page(s) 1296-1305, ISSN 2157-6564
DOI: 10.1002/sctm.19-0043

Study on the mixing and migration behavior of micron-size particles in acoustofluidics

Author(s): Pierre Gelin, Özlem Sardan Sukas, Karine Hellemans, Dominique Maes, Wim De Malsche
Published in: Chemical Engineering Journal, Issue 369, 2019, Page(s) 370-375, ISSN 1385-8947
DOI: 10.1016/j.cej.2019.03.004

Report of the Key Opinion Leaders Meeting on Stem Cell-derived Beta Cells

Author(s): Jon Odorico, James Markmann, Douglas Melton, Julia Greenstein, Albert Hwa, Cristina Nostro, Alireza Rezania, Jose Oberholzer, Daniel Pipeleers, Luhan Yang, Chad Cowan, Danwei Huangfu, Dieter Egli, Uri Ben-David, Ludovic Vallier, Shane T. Grey, Qizhi Tang, Bart Roep, Camilo Ricordi, Ali Naji, Giuseppe Orlando, Daniel G. Anderson, Mark Poznansky, Barbara Ludwig, Alice Tomei, Dale L. Greiner, Melanie
Published in: Transplantation, Issue 102/8, 2018, Page(s) 1223-1229, ISSN 0041-1337
DOI: 10.1097/tp.0000000000002217

Epitope Stealing as a Mechanism of Dominant Protection by HLA-DQ6 in Type 1 Diabetes

Author(s): Menno van Lummel, David T.P. Buis, Cherish Ringeling, Arnoud H. de Ru, Jos Pool, George K. Papadopoulos, Peter A. van Veelen, Helena Reijonen, Jan W. Drijfhout, Bart O. Roep
Published in: Diabetes, Issue 68/4, 2019, Page(s) 787-795, ISSN 0012-1797
DOI: 10.2337/db18-0501

Antigen-based immune modulation therapy for type 1 diabetes: the era of precision medicine

Author(s): Bart O Roep, Daniel C S Wheeler, Mark Peakman
Published in: The Lancet Diabetes & Endocrinology, Issue 7/1, 2019, Page(s) 65-74, ISSN 2213-8587
DOI: 10.1016/s2213-8587(18)30109-8

Multidimensional analyses of proinsulin peptide-specific regulatory T cells induced by tolerogenic dendritic cells

Author(s): Jessica S. Suwandi, Sandra Laban, Kincsὅ Vass, Antoinette Joosten, Vincent van Unen, Boudewijn P.F. Lelieveldt, Thomas Höllt, Jaap Jan Zwaginga, Tatjana Nikolic, Bart O. Roep
Published in: Journal of Autoimmunity, Issue 107, 2020, Page(s) 102361, ISSN 0896-8411
DOI: 10.1016/j.jaut.2019.102361

Heterogeneity of Human Pancreatic Islet Isolation Around Europe

Author(s): Rita Nano, Julie A. Kerr-Conte, Hanne Scholz, Marten Engelse, Marie Karlsson, Frantisek Saudek, Domenico Bosco, Barbara Antonioli, Federico Bertuzzi, Paul R.V. Johnson, Barbara Ludwing, Zhidong Ling, Diedert L. De Paep, Bart Keymeulen, François Pattou, Thierry Berney, Olle Korsgren, Eelco de Koning, Lorenzo Piemonti
Published in: Transplantation, Issue 104/1, 2020, Page(s) 190-196, ISSN 0041-1337
DOI: 10.1097/tp.0000000000002777

A viral link for type 1 diabetes

Author(s): Bart O. Roep
Published in: Nature Medicine, Issue 25/12, 2019, Page(s) 1816-1818, ISSN 1078-8956
DOI: 10.1038/s41591-019-0689-7

Transplant Site Influences the Immune Response After Islet Transplantation

Author(s): Elisa Cantarelli, Antonio Citro, Silvia Pellegrini, Alessia Mercalli, Raffaella Melzi, Erica Dugnani, Tatiana Jofra, Georgia Fousteri, Anna Mondino, Lorenzo Piemonti
Published in: Transplantation, Issue 101/5, 2017, Page(s) 1046-1055, ISSN 0041-1337
DOI: 10.1097/TP.0000000000001462

Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio

Author(s): Annelien Van Dalem, Simke Demeester, Eric V. Balti, Bart Keymeulen, Pieter Gillard, Bruno Lapauw, Christophe De Block, Pascale Abrams, Eric Weber, Ilse Vermeulen, Pieter De Pauw, Daniël Pipeleers, Ilse Weets, Frans K. Gorus
Published in: PLOS ONE, Issue 11/12, 2016, Page(s) e0166702, ISSN 1932-6203
DOI: 10.1371/journal.pone.0166702

Immunological Issues After Stem Cell-Based β Cell Replacement

Author(s): Valeria Sordi, Silvia Pellegrini, Lorenzo Piemonti
Published in: Current Diabetes Reports, Issue 17/9, 2017, ISSN 1534-4827
DOI: 10.1007/s11892-017-0901-4

Antiinflammatory strategies in intrahepatic islet transplantation

Author(s): A. Citro, E. Cantarelli, S. Pellegrini, E. Dugnani, L. Piemonti
Published in: Transplantation, 2017, Page(s) 1, ISSN 0041-1337
DOI: 10.1097/TP.0000000000001925

Autoimmunity against a defective ribosomal insulin gene product in type 1 diabetes

Author(s): Maria J L Kracht, Menno van Lummel, Tatjana Nikolic, Antoinette M Joosten, Sandra Laban, Arno R van der Slik, Peter A van Veelen, Françoise Carlotti, Eelco J P de Koning, Rob C Hoeben, Arnaud Zaldumbide, Bart O Roep
Published in: Nature Medicine, Issue 23/4, 2017, Page(s) 501-507, ISSN 1078-8956
DOI: 10.1038/nm.4289

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression

Author(s): Dae Hae Lee, Bart Keymeulen, Robert Hilbrands, Zhidong Ling, Ursule Van de Velde, Daniel Jacobs-Tulleneers-Thevissen, Geert Maleux, Bruno Lapauw, Laurent Crenier, Christophe De Block, Chantal Mathieu, Daniel Pipeleers, Pieter Gillard
Published in: Transplantation, Issue 101/9, 2017, Page(s) 2218-2227, ISSN 0041-1337
DOI: 10.1097/TP.0000000000001543

Direct effect of glucocorticoids on glucose-activated adult rat β-cells increases their cell number and their functional mass for transplantation

Author(s): Zerihun Assefa, Sarah Akbib, Astrid Lavens, Geert Stangé, Zhidong Ling, Karine H. Hellemans, Daniel Pipeleers
Published in: American Journal of Physiology - Endocrinology And Metabolism, Issue 311/4, 2016, Page(s) E698-E705, ISSN 0193-1849
DOI: 10.1152/ajpendo.00070.2016

HLA-A*24 Carrier Status and Autoantibody Surges Posttransplantation Associate With Poor Functional Outcome in Recipients of an Islet Allograft

Author(s): Simke Demeester, Else M. Balke, Bart J. Van der Auwera, Pieter Gillard, Robert Hilbrands, DaHae Lee, Ursule Van de Velde, Zhidong Ling, Bart O. Roep, Daniel G. Pipeleers, Frans K. Gorus, Bart Keymeulen
Published in: Diabetes Care, Issue 39/6, 2016, Page(s) 1060-1064, ISSN 0149-5992
DOI: 10.2337/dc15-2768

Stem cells to restore insulin production and cure diabetes

Author(s): V. Sordi, S. Pellegrini, M. Krampera, P. Marchetti, A. Pessina, G. Ciardelli, G. Fadini, C. Pintus, G. Pantè, L. Piemonti
Published in: Nutrition, Metabolism and Cardiovascular Diseases, Issue 27/7, 2017, Page(s) 583-600, ISSN 0939-4753
DOI: 10.1016/j.numecd.2017.02.004

Serum Cytokines as Biomarkers in Islet Cell Transplantation for Type 1 Diabetes

Author(s): Cornelis R. van der Torren, Annemarie A. Verrijn Stuart, DaHae Lee, Jenny Meerding, Ursule van de Velde, Daniel Pipeleers, Pieter Gillard, Bart Keymeulen, Wilco de Jager, Bart O. Roep
Published in: PLOS ONE, Issue 11/1, 2016, Page(s) e0146649, ISSN 1932-6203
DOI: 10.1371/journal.pone.0146649

Heterogeneity in the Beta-Cell Population: a Guided Search Into Its Significance in Pancreas and in Implants

Author(s): Daniel Pipeleers, Ines De Mesmaeker, Thomas Robert, Freya Van Hulle
Published in: Current Diabetes Reports, Issue 17/10, 2017, ISSN 1534-4827
DOI: 10.1007/s11892-017-0925-9

Correction: Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio

Author(s): Annelien Van Dalem, Simke Demeester, Eric V. Balti, Bart Keymeulen, Pieter Gillard, Bruno Lapauw, Christophe De Block, Pascale Abrams, Eric Weber, Ilse Vermeulen, Pieter De Pauw, Daniël Pipeleers, Ilse Weets, Frans K. Gorus
Published in: PLOS ONE, Issue 12/6, 2017, Page(s) e0179108, ISSN 1932-6203
DOI: 10.1371/journal.pone.0179108

Twenty-Year Progression Rate to Clinical Onset According to Autoantibody Profile, Age, and HLA-DQ Genotype in a Registry-Based Group of Children and Adults With a First-Degree Relative With Type 1 Diabetes

Author(s): Frans K. Gorus, Eric V. Balti, Anissa Messaaoui, Simke Demeester, Annelien Van Dalem, Olivier Costa, Harry Dorchy, Chantal Mathieu, Luc Van Gaal, Bart Keymeulen, Daniël G. Pipeleers, Ilse Weets
Published in: Diabetes Care, Issue 40/8, 2017, Page(s) 1065-1072, ISSN 0149-5992
DOI: 10.2337/dc16-2228

MicroRNA expression profiles of human iPSCs differentiation into insulin-producing cells

Author(s): Guido Sebastiani, Marco Valentini, Giuseppina Emanuela Grieco, Giuliana Ventriglia, Laura Nigi, Francesca Mancarella, Silvia Pellegrini, Gianvito Martino, Valeria Sordi, Lorenzo Piemonti, Francesco Dotta
Published in: Acta Diabetologica, Issue 54/3, 2017, Page(s) 265-281, ISSN 0940-5429
DOI: 10.1007/s00592-016-0955-9

Tolerance Induction and Reversal of Diabetes in Mice Transplanted with Human Embryonic Stem Cell-Derived Pancreatic Endoderm

Author(s): Gregory L. Szot, Mahesh Yadav, Jiena Lang, Evert Kroon, Justin Kerr, Kuniko Kadoya, Eugene P. Brandon, Emmanuel E. Baetge, Hélène Bour-Jordan, Jeffrey A. Bluestone
Published in: Cell Stem Cell, Issue 16/2, 2015, Page(s) 148-157, ISSN 1934-5909
DOI: 10.1016/j.stem.2014.12.001

Immunogenicity of human embryonic stem cell-derived beta cells

Author(s): Cornelis R. van der Torren, Arnaud Zaldumbide, Gaby Duinkerken, Simone H. Brand-Schaaf, Mark Peakman, Geert Stangé, Laura Martinson, Evert Kroon, Eugene P. Brandon, Daniel Pipeleers, Bart O. Roep
Published in: Diabetologia, Issue 60/1, 2017, Page(s) 126-133, ISSN 0012-186X
DOI: 10.1007/s00125-016-4125-y

Development of an Enhanced Sensitivity Bead-Based Immunoassay for Real-Time In Vivo Detection of Pancreatic β-Cell Death

Author(s): Olivier R. Costa, Geert Stangé, Katrijn Verhaeghen, Benedicte Brackeva, Ellen Nonneman, Christiane S. Hampe, Zhidong Ling, Daniel Pipeleers, Frans K. Gorus, Geert A. Martens
Published in: Endocrinology, Issue 156/12, 2015, Page(s) 4755-4760, ISSN 0013-7227
DOI: 10.1210/en.2015-1636