Development of beta cell replacement therapy for type 1 diabetes
Project background:
A cure for type 1 diabetes (T1D) requires the reconstitution of a functional beta cell mass, either through regeneration (of the non-functional or lost beta cells) or by replacement (of isolated islets or stem-cell derived islets). Beta cell replacement therapy by clinical islet transplantation is a minimally invasive procedure that has evolved as a safe and efficient treatment option for patients with T1D with impaired hypoglycaemia awareness. Since the first clinical islet transplantation was performed in 1977, more than 4000 islet transplant procedures have been performed worldwide. OUS has performed the procedure since 2001 in collaboration with the Nordic Network for Clinical Islet Transplantation. Identify strategies that significantly improve the isolation process, survival and function of the islets, and establishing an extrahepatic transplant site would likely have a major impact on long-term outcomes after beta cell replacement therapy. Below is the project we currently focus on.
Clinical projects:
• Improving islet isolation and transplantation protocols in clinical practice
• Pancreatic islet auto transplantation in patients following total (sub-) pancreatomy (in collaboration with Dr. Anne Waage, Department of Gastroenterology, OUS)
Experimental projects:
• Preventing islet inflammatory stress response and beta cell mass loss
• Preserve beta cells in new onset of type 1 diabetes by treatment with adult stem cells (ASC, DSC)
• Direct beta cell differentiation from human iPS cells
• Transdifferentiation of ductal progenitor cells into islet-like cells
• Development of a bioartificial pancreas by 3D bioprinting technology
• Develop pancreas-on-a-chip technology
Publications 2021:
Abadpour S, Niemi EM, Strid Orrhult L, Nogueira LP, Haugen HJ, Josefsen D, Kvalheim G, Krauss S, Gatenholm P, Scholz H. 307.7: 3D Bioprinting of Functional Islets With Adipose-derived Stromal Cells in an Alginate/Nanocellulose Scaffold. Transplantation. 2021 Dec 1;105(12S1):S25. doi: 10.1097/01.tp.0000804424.50335.7e. PMID: 34908333.
Berishvili E, Casiraghi F, Amarelli C, Scholz H, Piemonti L, Berney T, Montserrat N. Mini-organs forum: how to advance organoid technology to organ transplant community. Transpl Int. 2021 Sep;34(9):1588-1593. doi: 10.1111/tri.13988. PMID: 34448263.
Piemonti L, Andres A, Casey J, de Koning E, Engelse M, Hilbrands R, Johnson P, Keymeulen B, Kerr-Conte J, Korsgren O, Lehmann R, Lundgren T, Maffi P, Pattou F, Saudek F, Shaw J, Scholz H, White S, Berney T. US food and drug administration (FDA) panel endorses islet cell treatment for type 1 diabetes: A pyrrhic victory? Transpl Int. 2021 Jul;34(7):1182-1186. doi: 10.1111/tri.13930. Epub 2021 Jun 11. PMID: 34048106.
Nordheim E, Lindahl JP, Carlsen RK, Åsberg A, Birkeland KI, Horneland R, Boye B, Scholz H, Jenssen TG. Patient selection for islet or solid organ pancreas transplantation: experiences from a multidisciplinary outpatient-clinic approach. Endocrine Connections. 2021;10(2):230-9. doi: 10.1530/EC-20-0519 PubMed 33544090
Zhou AX, Mondal T, Tabish AM, Abadpour S, Ericson E, Smith DM, Knöll R, Scholz H, Kanduri C, Tyrberg B. The long noncoding RNA TUNAR modulates Wnt signaling and regulates human β-cell proliferation. Am J Physiol Endocrinol Metab 2021 Apr 1;320(4):E846-E857.DOI: 10.1152/ajpendo.00335.2020 PubMed 33682459
Co-investigators/participants:
Prof. Trond Geir Jenssen, MD, PhD and Prof. Kåre Birkeland, MD, PhD, UiO/OUS
Shadab Abadpour MSc, PhD, Postdoctor OUS/UiO
Ragnhild Fjukstad, Biomedical Laboratory Scientist OUS
Marina Katavic, MSc, Biomedical Laboratory Scientist, OUS
Merete Høyem, Research technician OUS
Section for Transplantation Surgery, OUS (Prof. Pål Dag Line, Morten Hagness, MD, PhD, Kristine Fasting, MD)
External collaborators:
The Nordic Network for Clinical Islet transplantation and Uppsala University, Uppsala, Sweden. Main researcher: Prof. Olle Korsgren (Human islet isolation, clinical trials and diabetes research).
Chalmers University of Technology, Gotenburg, Sweden. Main researcher: Prof. Paul Gatenholm (3D bioprinting of cells)
MERLN Institute for technology-inspired regenerative medicine, Maastricht University. Main researcher: Dr. A.A van Apeldoorn (Develop a 3D ex vivo model of human islets)
European Pancreas and Islet Transplant Association Consortioum (EPITA)
