Årsrapport Scholz group IKF

Type 1 diabetes (T1D) is an autoimmune disease caused by destruction of the alpha- and beta cells in the pancreas. Prevention of T1D is hampered by the fact that the actual mechanism of cell destruction is largely unknown. Standard of care in T1D is life-long therapy with exogenous insulin. In spite of optimal insulin therapy (including digital insulin pump devices and subcutaneous glucose sensors), periods of hyperglycemia induce serious vascular- and neurological complications, such as accelerated arteriosclerosis, kidney failure and impaired vision.

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Clinical islet transplantation is an alternative therapy for those T1D patients whose disease cannot be effectively managed with current methods of exogenous insulin administration. In terms of improving glycemic control and reducing life-threatening episodes of hypoglycemia, islet transplantation is highly successful, but the long-term efficacy is still too low and further refinement of the treatment is highly needed.

The research group is responsible for human islet isolation from deceased donors for clinical islet transplantation of patients suffering from severe type 1 diabetes in Norway and does this in close collaboration with the Nordic Network for Clinical Islet transplantation and the Uppsala group (led by Prof. Olle Korsgren). The islet isolation facility is located at department for Cellular Therapy at Radiumhospitalet (led by Dr. Gunnar Kvalheim).

The research group has a clear translational approach with projects ranging from clinical trials and outcome studies, experimental islets biology and cell transplant studies in small animal models, and advanced in vitro studies.

AIMS

Specific aim:

Improvement and optimization of islet isolation, transplantation and clinical outcome

Long term objective for the group:

To develop new cell-based therapies, and tissue substitutes to treat and cure diabetes in humans

PROJECTS

  • Improvements of pancreatic islet isolation techniques and isolation outcome of human islets  
  • Investigate the intracellular drug-drug interactions of immunosuppressants in adult stem cells and human islets.
  • Regenerative/repair of the endocrine compartment of the pancreas using adult stem cells.
  • Development of 3D Bioprinting of biomimetic pancreas to treat diabetes
  • Established a therapeutic biobank of adult stem cells for treatment of diabetes and diabetes related complications

RECENT ACHIEVEMENTS / Highlights of the year

Dr. Hanne Scholz become principle investigator (Scholz lab) at the Center of Excellent (SFF) “Organ on a chip” led by Stefan Krauss. The project outline and aims can be further explored at Link www: jeg setter inn linken til SFFét, kommer i løpet av uken.

Kristine Kloster-Jensen, MD delivered her thesis entitled “Functional in vitro studies of immunosuppressive agents in human pancreatic islets” to Institute of Clinical Medicine, UiO in December 2017.

PhD student Shadab Abadpour received the 2017 IPITA-TTS Young Investigator Scientific and travel award, IPITA congress Oxford 20-23 June, 2018

Dr. Hanne Scholz was elected for councilor of the International Islet and Pancreas Transplantation Association (IPITA) (2017-2021)

Popular scientific contributions:

  • Hanne Scholz has contributed to the online learning platform of European Society for Organ Transplantation (ESOT): “THE ISLET ISOLATION LAB” in Milan Oct 2017.
  • Forskningsykehuset OUS Blog 21.9 2017 «Regenerativ medisin - En fot innenfor i fremtidens medisin» by Hanne Scholz
  • Organizing the young Investigators activities i) Pre-congress Career Development Symposia, ii) Young Investigators Social Evening, iii) Morning Discussion Run, iv) Young Investigator Oral Prize Session, v) Post-congress Young Investigator DRWF Public Engagement Event at IPITA Congress Oxford June 20-23, 2017
  • Lecture at OUS Research Seminar May 2nd 2017: Title: Islet transplantation in type 1 diabetes indications and results (by Hanne Scholz)
  •  OUS Stabsmøte 29.09.17 Institutt for Kirurgisk Forsking. «Transplantasjon av insulinproduserende celler de neste 10 årene» (by Hanne Scholz)

National and international presentations:

Oral presentations

  • PhD student Shadab Abadpour “LIGHT/TNFSF14 and glucotoxcicity induce an adverse effect on human islets through elevation of islet dysfunction and apoptosis” 7th EPITA Symposium & 36th AIDPIT Workshop, Jan 2017 Igls, Austria
  • PhD student Shadab Abadpour “Transdifferentiation of isolated human exocrine cells to beta-like cells.” IPITA, June 2017 Oxford, UK.
  • PhD student Shadab Abadpour “Interlukin-22 reverses human islets dysfunction and apoptosis triggered by hyperglycemia and LIGHT.” International Pancreas and Islet Transplantation Association Congress, June 2017 Oxford, UK.
  • Dr. Hanne Scholz. “GPR44 inhibition improves islets function and survival in transplanted human islets.” IPITA, June 2017 Oxford, UK.

Posters

  • PhD student Simen W. Schive. Human adipose derived mesenchymal stem cells respond to short term hypoxia by secreting factors beneficial for human islets in vitro and potentiate anti-diabetic effect in vivo. 7th EPITA Symposium & 36th AIDPIT Workshop, Jan 2017 Igls, Austria.

COLLABORATORS

National:

  • Helge Ræder, KG Jebsen Center for Diabetes Research, University of Bergen
  • Håvard Haugen, Department of Biomaterials, Institute of Clinical Dentistry Faculty of Dentistry, UiO.
  • Valdemar Grill, Department of Cancer Research, NTNU, Trondheim.
  • Bente Halvorsen, Research Institute for Internal Medicine, OUS.
  • Pål Aukrust, Research Institute for Internal Medicine, OUS.
  • Arne Ynderstad, Research Institute for Internal Medicine, OUS.
  • Hanne Løvdal Gulseth, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Aker Hospital, OUS

International:

  • University of Oxford, United Kingdom. Nuffield Department of Surgical Sciences, Oxford Centre for Diabetes. Main researcher: Prof. Paul R.V. Johnson and Senior scientist Danel Brandhorst
  • Astra Zeneca R&D, CVMD iMed Bioscience, Mølndal, Sweden. Main researcher: Maria Sørhede Winzell
  • Uppsala University, Rudbeck Life Science. Main Researcher Prof. Olle Korsgren.
  • Chalmers University of Technology, Gothenburg, Sweden. Main Researcher Prof. Paul Gatenholm

Active member in Network:

Nordic Network for Clinical Islet Transplantation link Nordic Network for Clinical Islet Transplantation
Oslo Regenerative Medicine Cluster (OUS Focus Research area 2014-2018). Leader Hanne Scholz
Scandiatransplant -The Nordic Pancreas and Islet Transplant Group (NπTG) link Scandiatransplant
International Pancreas & Islet Transplant Association (IPITA)- link IPITA
The Norwegian Center for Stem Cell Research link The Norwegian Center for Stem Cell Reseach
Oslo Diabetes Research Centre link Oslo Diabetes Reseach Center

Publications 2017:

  1. Abadpour S, Gopel SO, Schive SW, Korsgren O, Foss A, Scholz H. Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis. Sci Rep. 2017;7(1):1575.
  2. Hals I, Ohki T, Singh R, Ma Z, Bjorklund A, Balasuriya C, et al. Hyperoxia reduces insulin release and induces mitochondrial dysfunction with possible implications for hyperoxic treatment of neonates. Physiol Rep. 2017;5(19).
  3. Schive SW, Foss A, Sahraoui A, Kloster-Jensen K, Hafsahl G, Kvalheim G, et al. Cost and clinical outcome of islet transplantation in Norway 2010-2015. Clin Transplant. 2017;31(1).
  4. Schive SW, Mirlashari MR, Hasvold G, Wang M, Josefsen D, Gullestad HP, et al. Human Adipose-Derived Mesenchymal Stem Cells Respond to Short-Term Hypoxia by Secreting Factors Beneficial for Human Islets In Vitro and Potentiate Antidiabetic Effect In Vivo. Cell Med. 2017;9(3):103-16.
  5. Schuetz C, Anazawa T, Cross SE, Labriola L, Meier RPH, Redfield RR 3rd, Scholz H, Stock PG, Zammit NW; IPITA YIC Young Investigator Committee. ß cell replacement therapy: the next 10 years. Transplantation. 2018 Feb;102(2):215-229.
  6. Vethe H, Bjorlykke Y, Ghila LM, Paulo JA, Scholz H, Gygi SP, et al. Probing the missing mature beta-cell proteomic landscape in differentiating patient iPSC-derived cells. Sci Rep. 2017;7(1):4780.
  7. Brandhorst D, Brandhorst H, Acreman S, Schive SW, Bjørnson Scholz H, Johnson PRV. Hypoxia-Induced Damage in Human Islets Is Reduced With the Use of Mesenchymal Stem Cell-Preconditioned Medium. Transplant Proc. 2017 Dec;49(10):2330-2332
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