Issue 4 - Volume 1 - September 2023
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This quarterly newsletter highlights the latest and most relevant publications in our field, as well as association news, and updates on meetings and educational activities.

In This Issue

  • Report on the 4th Summit on Stem Cell-Derived Beta Cells
  • IPITA-IXA-CTRMS 2023 Joint Congress
  • Recent Publications of Interest
This bulletin was created thanks to the outstanding contributions of Giuseppe Orlando, Bob Stratta, Jon Odorico, Andrea Peloso, Melina Bellin, Monica Westley and Silke Niederhaus.

Steven Paraskevas

Editor, Beta-Cell Bulletin
IPITA Education Committee

Report on the 4th Summit on Stem Cell-Derived Beta Cells

IPITA continues to be at the vanguard of beta cell replacement therapy for treating diabetes, and this was again evident in their sponsorship and the success of the 4th Summit on Stem Cell-Derived Beta Cells that was held in Cambridge, MA, USA on April 24-25, 2023. With the co-sponsorship of the Juvenile Diabetes Research Foundation and the Harvard Stem Cell Institute, the Summit brought over 180 top experts together to share ongoing work aimed towards refining stem cell islets as a biological therapy for T1D and to chart the path forward for the field. The Summit was focused on gaining insights from islet biology including single-cell multi-omics, and how this knowledge might be applied toward optimizing differentiation protocols and deriving methods to eliminate off-target cells. The meeting also included sessions devoted to discussing technologies designed to eliminate the need for immunosuppression or reduce immunogenicity, such as CRISPR genome engineering. An update was provided on an ongoing clinical trial and over 30 abstracts were presented. Finally, a critical aspect of the meeting was a panel discussion on the eligibility criteria for stem cell islet trials that involved key stakeholders including patients, endocrinologists, regulatory experts, and scientists.

IPITA-IXA-CTRMS 2023 Joint Congress

The IPITA-IXA-CTRMS 2023 Joint Congress will take place in San Diego on October 26-29. The conference will feature an outstanding program and will present the state of the art of regenerative medicine technologies as they can be applied not only to beta cell replacement but to transplant medicine, more broadly. Leading experts and opinion leaders from all over the world will present the latest data and address important needs in clinical and experimental transplant therapy. Specific sessions will be devoted to hot research in whole-organ pancreas transplantation, islet transplantation, stem cell therapy, xenotransplantation and transplant biology. It’s a very exciting time to be involved in transplant sciences and this conference will prove that! At the same time, we are very excited for the opportunity to meet again after the pandemic and we are all looking forward to gathering in beautiful San Diego, at the best time of the year to be in the city.

Recent Publications of Interest

Pancreas Transplantation

OPTN/SRTR 2021 Annual Data Report: Pancreas
Raja Kandaswamy, Peter G Stock, Jonathan M Miller, Joann White , Sarah E Booker, Ajay K Israni, Jon J Snyder
Am J Transplant. 2023 Feb;23(2 Suppl 1):S121-S177. doi: 10.1016/j.ajt.2023.02.005.
Recipient and graft outcomes in simultaneous kidney and pancreas transplantation with steroid avoidance in the United States
Adam Cerise, Tamer Shaker, Phuoc LeNguyen, Anant Dinesh, Scott Jackson, Raja Kandaswamy, Samy Riad.
Transplantation. 2023 Feb 1;107(2):521-528. doi: 10.1097/TP.0000000000004295. Epub 2022 Sep 30.
Heparin thromboprophylaxis in simultaneous pancreas-kidney transplantation. A systematic review and meta-analysis of observational studies
Erica Ai Li, Kaveh Farrokhi, Max Y Zhang, Juliano Offerni, Patrick P Luke, Alp Sener
Transpl Int. 2023 Feb 1;36:10442. doi: 10.3389/ti.2023.10442. eCollection 2023.
Metabolic outcomes after pancreas transplant alone from donation after circulatory death donors – The UK transplant registry analysis
Jeevan Prakash Gopal, Adam McLean, Anand Muthusamy
Transpl Int. 2023 May 17;36:11205. doi: 10.3389/ti.2023.11205. eCollection 2023.
Six-month abdominal transplant recipient outcomes from donation after circulatory death heart donors: a retrospective analysis by procurement technique
Anji Wall, Matthew Rosenzweig, Gregory J McKenna, Tsung-Wei Ma, Sumeet K Asrani, Giuliano Testa
Am J Transplant. 2023 Jul;23(7):987-995. doi: 10.1016/j.ajt.2023.04.021. Epub 2023 Apr 21.
A Multi-Modal Approach to Islet and Pancreas Transplantation with Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients with Type I Diabetes
Steven A Wisel, Andrew M Posselt, Gregory L Szot, Miguel Nunez, Keli Santos-Parker, James M Gardner, Giulia Worner, Garrett R Roll, Shareef Syed, Yvonne Kelly, Casey Ward, Medhi Tavakol, Kristina Johnson, Umesh Masharani, Peter G Stock
Transpl Int. 2023 Jun 8;36:11367. doi: 10.3389/ti.2023.11367.
Normothermic regional perfusion can improve both utilization and outcomes in DCD liver, kidney, and pancreas transplantation
Gabriel C Oniscu, Jennifer Mehew, Andrew J Butler, Andrew Sutherland, Rohit Gaurav, Rachel Hogg, Ian Currie, Mark Jones, Christopher JE Watson
Transplantation. 2023 Feb 1;107(2):438-448. doi: 10.1097/TP.0000000000004280. Epub 2023 Jan 26.
The best insulin delivery is a human pancreas
Kasi McCune, Nina Owen-Simon, Geoffrey K Dube, Lloyd E Ratner
Clin Transplant. 2023 Apr;37(4):e14920. doi: 10.1111/ctr.14920. Epub 2023 Feb 13.
Comprehensive review: Frailty in pancreas transplant candidates and recipients
Ronald F Parsons, Ekamol Tantisattamo, Wisit Cheungpasitporn, Arpita Basu, Yee Lu, Krista L Lentine, Kenneth J Woodside, Neeraj Singh, Joseph Scalea, Tarek Alhamad, Ty B Dunn, Franco H Cabeza Rivera, Sandesh Parajuli, Martha Pavlakis, Matthew Cooper
Clin Transplant. 2023 Feb;37(2):e14899. doi: 10.1111/ctr.14899. Epub 2023 Jan 13.
Early Increases in Posttransplant Pancreatic Enzymes Are Associated With Surgical Complications But Not Graft Failure Among Pancreas Transplant Recipients
Sandesh Parajuli, Glen E Leverson, Dixon B Kaufman, Arjang Djamali, Bridget M Welch, Hans W Sollinger, Didier A Mandelbrot, Jon S Odorico
Pancreas. 2022 Nov-Dec;51(10):1381-1387. doi: 10.1097/MPA.0000000000002187.
Higher Fasting Pretransplant C-peptide Levels in Type 2 Diabetics Undergoing Simultaneous Pancreas-kidney Transplantation Are Associated With Posttransplant Pancreatic Graft Dysfunction
Sandesh Parajuli, Didier Mandelbrot, David Aufhauser, Dixon Kaufman, Jon Odorico
Transplantation. 2023 Apr 1;107(4):e109-e121. doi:10.1097/TP.0000000000004489. Epub 2023 Jan 5.
Pancreas Transplantation for Type 2 Diabetes: A Systematic Review, Critical Gaps in the Literature, and a Path Forward
Dominic Amara, Keith S Hansen, Sophie A Kupiec-Weglinski, Hillary J Braun, Ryutaro Hirose, Joan F Hilton, Michael R Rickels, Jon S Odorico, Peter G Stock
Transplantation. 2022 Oct 1;106(10):1916-1934. doi: 10.1097/TP.0000000000004113. Epub 2022 May 5.
Post-pancreatic transplant enteric leaks: The role of the salvage operation
Vidya A Fleetwood, Cody Falls, Jakob Ohman, Antony Aziz, Lily Stalter, Glen Leverson, Bridget Welch, Dixon B Kaufman, David P Al-Adra, Jon S Odorico
Am J Transplant. 2022 Aug;22(8):2052-2063. doi: 10.1111/ajt.17094. Epub 2022 Jun 7.
Utility of Protocol Pancreas Biopsies for De Novo Donor-specific Antibodies
Sandesh Parajuli, Didier Mandelbrot, Jon Odorico
Transplant Direct. 2022 Feb 11;8(3):e1287. doi: 10.1097/TXD.0000000000001287. eCollection 2022 Mar.
Pancreas and Islet Transplantation: comparative outcome analysis of a single-centre cohort over 20-years
Marfil-Garza BA, Hefler J, Verhoeff K, et al.
Ann Surg. 2023 Apr 1;277(4):672-680. doi: 10.1097/SLA.0000000000005783. Epub 2022 Dec 20.

Islet Transplantation

Diagnosis and treatment of allograft rejection in islet transplantation
Cyril P Landstra, Michiel F Nijhoff, Dave L Roelen, Aiko PJ de Vries, Eelco JP de Koning
Am J Transplant. 2023 Jun 10;S1600-6135(23)00523-3. doi: 10.1016/j.ajt.2023.05.035. Online ahead of print.
Modeling Type 1 Diabetes progression from single-cell transcriptomic measurements in human islets
Abhijeet R. Patil, Jonathan Schug, Chengyang Liu, Deeksha Lahori, Hélène C. Descamps, The Human Pancreas Analysis Consortium, Ali Naji, Klaus H. Kaestner, Robert B. Faryabi, Golnaz Vahedi.
Pancreatic islet cell stress induced by insulin-degrading enzyme deficiency promotes islet regeneration and protection from autoimmune diabetes
Shuaishuai Zhu, Emmanuelle Waeckel-Énée, Anna Moser, Marie-Andrée Bessard, Kevin Roger, Joanna Lipecka, Ayse Yilmaz, Barbara Bertocci, Julien Diana, Benjamin Saintpierre, Ida Chiara Guerrera, Stefania Francesconi, François-Xavier Mauvais, Peter van Endert
Association between primary graft function and 5-year outcomes of islet allogeneic transplantation in type 1 diabetes: a retrospective, multicentre, observational cohort study in 1210 patients from the Collaborative Islet Transplant Registry
Mikaël Chetboun, Elodie Drumez, Cassandra Ballou, Mehdi Maanaoui, Elizabeth Payne, Franca Barton, Julie Kerr-Conte, Marie-Christine Vantyghem, Lorenzo Piemonti, Michael R Rickels, Julien Labreuche, François Pattou; Collaborative Islet Transplant Registry (CITR) Investigators study group
Lancet Diabetes Endocrinol. 2023 Jun;11(6):391-401. doi: 10.1016/S2213-8587(23)00082-7. Epub 2023 Apr 24.
Monitoring β-Cell Survival After Intrahepatic Islet Transplantation Using Dynamic Exendin PET Imaging: A Proof-of-Concept Study in Individuals with Type 1 Diabetes
Theodorus JP Jansen, Mijke Buitinga, Marti Boss, Michiel F Nijhoff, Maarten Brom, Bastiaan E de Galan, Marinette van der Graaf, Sebastiaan van Koeverden, Marie-Christine Vantyghem, Amandine Beron, François Pattou, Marten A Engelse, Irina Velikyan, Olof Eriksson, Eelco JP de Koning, Martin Gotthardt
Diabetes. 2023 Jul 1;72(7):898-907. doi: 10.2337/db22-0884
A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment
Tasneem R Abdel-Karim, James S Hodges, Timothy L Pruett, Karthik V Ramanathan, Bernhard J Hering, Ty B Dunn, Varvara A Kirchner, Gregory J Beilman, Melena D Bellin
Pancreatology. 2023 Jan;23(1):57-64. doi: 10.1016/j.pan.2022.11.006. Epub 2022 Nov 24.
Long-term Outcomes with Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study
Michael R Rickels, Thomas L Eggerman, Levent Bayman, Julie C Qidwai, Rodolfo Alejandro, Nancy D Bridges, Bernhard J Hering, James F Markmann, Peter A Senior, Lawrence G Hunsicker; Clinical Islet Transplantation Consortium
Diabetes Care. 2022 Oct 17;45(12):2967–75. doi: 10.2337/dc21-2688. Epub ahead of print.
Factors associated with favorable 5 year outcomes in islet transplant alone recipients with type 1 diabetes complicated by severe hypoglycemia in the Collaborative Islet Transplant Registry
Bernhard J Hering, Cassandra M Ballou, Melena D Bellin, Elizabeth H Payne, Fouad Kandeel, Piotr Witkowski, Rodolfo Alejandro, Michael R Rickels, Franca B Barton
Diabetologia. 2023 Jan;66(1):163-173. doi: 10.1007/s00125-022-05804-4. Epub 2022 Oct 6.
Predicting endocrine function after total pancreatectomy and islet cell autotransplantation: A novel approach utilizing computed tomography texture analysis
Kevin M Turner, Shaun A Wahab, Aaron M Delman, John Brunner, Milton T Smith, Kyuran A Choe, Sameer H Patel, Syed A Ahmad, Gregory C Wilson
Surgery. 2023 Mar;173(3):567-573. doi: 10.1016/j.surg.2022.06.052.
Total Pancreatectomy with islet Autotransplantation as an Alternative to high-risk Pancreatojejunostomy after Pancreaticoduodenectomy: A Prospective Randomized Trial
Gianpaolo Balzano, Alessandro Zerbi, Francesca Aleotti, Giovanni Capretti, Raffella Melzi, Nicolò Pecorelli, Alessia Mercalli, Rita Nano, Paola Magistretti, Francesca Gavazzi, Francesco De Cobelli, Dario Poretti, Marina Scavini, Chiara Molinari, Stefano Partelli, Stefano Crippa, Paola Maffi, Massimo Falconi, Lorenzo Piemonti
Ann Surg. 2022 Sep 30;277(6):894¨C903. doi: 10.1097/SLA.0000000000005713. Epub ahead of print.

Regenerative Medicine

Validating expression of beta cell maturation-associated genes in human pancreas development
Daniel M Tremmel, Anna E Mikat, Sakar Gupta, Samantha A Mitchell, Andrew M Curran, Jenna A Menadue, Jon S Odorico, Sara Dutton Sackett
Front Cell Dev Biol. 22023 Feb 1;11:1103719. doi: 10.3389/fcell.2023.1103719. eCollection 2023.
Decorin improves human pancreatic β-cell function and regulates ECM expression in vitro
Max Urbanczyk, Abiramy Jeyagaran, Aline Zbinden, Chuan-En Lu, Julia Marzi, Laurence Kuhlburger, Sven Nahnsen, Shannon L Layland, Garry Duffy, Katja Schenke-Layland
Matrix Biol. 2023 Jan;115:160-183. doi: 10.1016/j.matbio.2022.12.005. Epub 2022 Dec 30.
The bioengineering of perfusable endocrine tissue with anastomosable blood vessels
Hiroki Yago, Jun Homma, Hidekazu Sekine, Yuhei Higashi, Hiroyuki Sakurai, Tatsuya Shimizu
Biofabrication. 2023 Jul 24. doi: 10.1088/1758-5090/ace9fc. Online ahead of print.
Human induced pluripotent stem cells (hiPSC), enveloped in elastin-like recombinamers for cell therapy of type 1 diabetes mellitus (T1D): preliminary data
Pia Montanucci, Teresa Pescara, Alessia Greco, Giuseppe Basta, Riccardo Calafiore
Front Bioeng Biotechnol. 2023 Apr 25;11:1046206. doi: 10.3389/fbioe.2023.1046206. eCollection 2023.
Islets in the body are never flat: transitioning from two-dimensional (2D) monolayer culture to three-dimensional (3D) spheroid for better efficiency in the generation of functional hPSC-derived pancreatic β cells in vitro
Abdoulaye Diane, Layla Ibrahim Mohammed, Heba H Al-Siddiqi
Cell Commun Signal. 2023 Jun 22;21(1):151. doi: 10.1186/s12964-023-01171-8.
Three-in-one customized bioink for islet organoid: GelMA/ECM/PRP orchestrate pro-angiogenic and immunoregulatory function
Biwen Zhu, Dongzhi Wang, Haopeng Pan, Tiancheng Gong, Qianqian Ren, Zhiwei Wang, Yibing Guo
Colloids Surf B Biointerfaces. 2023 Jan;221:113017. doi: 10.1016/j.colsurfb.2022.113017. Epub 2022 Nov 12.
In Vivo CaV3 Channel Inhibition Promotes Maturation of Glucose-Dependent Ca2+ Signaling in Human iPSC-Islets
Kaixuan Zhao, Yue Shi, Jia Yu, Lina Yu, Martin Köhler, Amber Mael, Anthony Kolton, Thomas Joyce, Jon Odorico, Per-Olof Berggren, Shao-Nian Yang
Biomedicines. 2023 Mar 7;11(3):807. doi: 10.3390/biomedicines11030807.
Directed self-assembly of a xenogeneic vascularized endocrine pancreas for type 1 diabetes
Antonio Citro, Alessia Neroni, Cataldo Pignatelli, Francesco Campo, Martina Policardi, Matteo Monieri, Silvia Pellegrini, Erica Dugnani, Fabio Manenti, Maria Chiara Maffia, Libera Valla, Elisabeth Kemter, Ilaria Marzinotto, Cristina Olgasi, Alessia Cucci, Antonia Follenzi, Vito Lampasona, Eckhard Wolf, Lorenzo Piemonti
Nat Commun. 2023 Feb 16;14(1):878. doi: 10.1038/s41467-023-36582-1.
Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation
Joshua M Gammon, Sean T Carey, Vikas Saxena, Haleigh B Eppler, Shannon J Tsai, Christina Paluskievicz, Yanbao Xiong, Lushen Li, Marian Ackun-Farmmer, Lisa H Tostanoski, Emily A Gosselin, Alexis A Yanes, Xiangbin Zeng, Robert S Oakes, Jonathan S Bromberg, Christopher M Jewell
Nat Commun. 2023 Feb 8;14(1):681. doi: 10.1038/s41467-023-36225-5.
Three-dimensional bioprinting of functional β-islet-like constructs
Shahram Parvaneh, Lajos Kemény, Ameneh Ghaffarinia, Reza Yarani, Zoltán Veréb
Int J Bioprint. 2023 Jan 9;9(2):665. doi: 10.18063/ijb.v9i2.665.
Matters arising: Insufficient evidence that pancreatic β cells are derived from adult ductal Neurog3-expressing progenitors
Judith Magenheim, Miguel Angel Maestro, Nadav Sharon, Pedro L Herrera, L Charles Murtaugh, Janel Kopp, Maike Sander, Guoqiang Gu, Douglas A Melton, Jorge Ferrer, Yuval Dor
Cell Stem Cell. 2023 Apr 6;30(4):488-497.e3. doi: 10.1016/j.stem.2023.03.003.
Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance
Dario Gerace, Quan Zhou, Jennifer Hyoje-Ryu Kenty, Adrian Veres, Elad Sintov, Xi Wang, Kyle R Boulanger, Hongfei Li, Douglas A Melton
Cell Rep Med. 2023 Jan 17;4(1):100879. doi: 10.1016/j.xcrm.2022.100879. Epub 2023 Jan 3.


3D Bioprinting for Pancreas Engineering/Manufacturing
Yukun Xu, Dabin Song, Xiaohong Wang
Polymers (Basel). 2022 Nov 25;14(23):5143. doi: 10.3390/polym14235143.
Pancreas transplantation: Current challenges, considerations, and controversies
Jonathan A Fridell, Robert J Stratta, Angelika C Gruessner
J Clin Endocrinol Metab. 2023 Feb 15;108(3):614-623. doi:10.1210/clinem/dgac644.
The pathogenic “symphony” in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas
Mark A Atkinson, Raghavendra G Mirmira
Cell Metab. 2023 Jul 17;S1550-4131(23)00228-0. doi: 10.1016/j.cmet.2023.06.018. Online ahead of print.
Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes
Nathaniel J Hogrebe, Matthew Ishahak, Jeffrey R Millman
Cell Stem Cell. 2023 May 4;30(5):530-548. doi: 10.1016/j.stem.2023.04.002.
Genetic Engineering of Immune Evasive Stem Cell-Derived Islets
Sara D Sackett, Samuel J Kaplan, Samantha A Mitchell, Matthew E Brown, Adam L Burrack, Shane Grey, Danwei Huangfu, Jon Odorico
Transpl Int. 2022 Dec 5;35:10817. doi: 10.3389/ti.2022.10817. eCollection 2022.
Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases: Workshop Proceedings
Teresa L Mastracci, Minoti Apte, Laufey T Amundadottir, Alexandra Alvarsson, Steven Artandi, Melena D Bellin, Ernesto Bernal-Mizrachi, Alejandro Caicedo, Martha Campbell-Thompson, Zobeida Cruz-Monserrate, Abdelfattah El Ouaamari, Kyle J Gaulton, Andrea Geisz, Mark O Goodarzi, Manami Hara, Rebecca L Hull-Meichle, Alexander Kleger, Alison P Klein, Janel L Kopp, Rohit N Kulkarni, Mandar D Muzumdar, Anjaparavanda P Naren, Scott A Oakes, Søren S Olesen, Edward A Phelps, Alvin C Powers, Cherie L Stabler, Temel Tirkes, David C Whitcomb, Dhiraj Yadav, Jing Yong, Norann A Zaghloul, Stephen J Pandol, Maike Sander
Diabetes. 2023 Apr 1;72(4):433-448. doi: 10.2337/db22-0942.
Regenerative medicine technologies applied to transplant medicine. An update
Astgik Petrosyan, Filippo Montali, Andrea Peloso, Antonio Citro, Lori N Byers, Catherine La Pointe, Mara Suleiman, Alice Marchetti, Eoin P Mcneill, Allison L Speer, Wai Hoe Ng, Xi Ren, Benedetta Bussolati, Laura Perin, Paolo Di Nardo, Vincenzo Cardinale, Jerome Duisit, Alexandra Rose Monetti, John Richard Savino, Amish Asthana, Giuseppe Orlando
Front Bioeng Biotechnol. 2022 Sep 28;10:1015628. doi: 10.3389/fbioe.2022.1015628. eCollection 2022.



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