Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice

Autor: Benjamin L. George, Yang Sun, Enrico Petretto, Anne-May Österholm, Xiaoran Chai, Miina K. Öhman, Kristmundur Sigmundsson, Molly M. Stevens, Manuel Patarroyo, Anna Domogatskaya, Ann-Sofie Nilsson, Aida Moreno-Moral, Li Yen Chong, Juha R.M. Ojala, Karl Tryggvason, Joseph A. M. Steele, Sergey Rodin, Sujoy Ghosh
Rok vydání: 2018
Předmět:
0301 basic medicine
Blood Glucose
Male
Necrosis
endocrine system diseases
Cell Culture Techniques
Islets of Langerhans Transplantation
beta-cell
MELLITUS
Mice
0302 clinical medicine
Laminin
Insulin
Cells
Cultured
GENE-EXPRESSION
geography.geographical_feature_category
biology
Diabetes
Islet
SHEETS
β-cell
Extracellular Matrix
medicine.anatomical_structure
Treatment Outcome
BASEMENT-MEMBRANE
SURVIVAL
medicine.symptom
Beta cell
Life Sciences & Biomedicine
medicine.drug
Biochemistry & Molecular Biology
endocrine system
STREPTOZOTOCIN
INHIBITION
Streptozocin
Diabetes Mellitus
Experimental
Andrology
03 medical and health sciences
Islets of Langerhans
Diabetes mellitus
LAMININS
medicine
Animals
Humans
Molecular Biology
Cell Proliferation
Transplantation
geography
Science & Technology
Pancreatic
business.industry
Pancreatic islets
Cell Biology
06 Biological Sciences
medicine.disease
Streptozotocin
Mice
Inbred C57BL
Macaca fascicularis
030104 developmental biology
biology.protein
business
INTEGRIN
030217 neurology & neurosurgery
BETA-CELL PROLIFERATION
Zdroj: Matrix biology : journal of the International Society for Matrix Biology. 70
ISSN: 1569-1802
Popis: The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1–3 cells in thickness and remained normoxic and functional for at least 7 days in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16 h. Transplantation of 110–150 mouse islets cultured on α5-laminin-coated polydimethylsiloxane membranes for 3–7 days normalized blood glucose already within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with α5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes.
Databáze: OpenAIRE
Externí odkaz: