Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells

• Published in: Diabetologia Vol. 55; no. 7; pp. 2016 - 2025
• Main Authors: Grouwels, G., Vasylovska, S., Olerud, J., Leuckx, G., Ngamjariyawat, A., Yuchi, Y., Jansson, L., Van de Casteele, M., Kozlova, E. N., Heimberg, H.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-07-2012; Springer; Springer Nature B.V
• Subjects: Animals; Beta cell; Biological and medical sciences; Blood Glucose - metabolism; Cell culture; Cell growth; Cell Proliferation; Cells, Cultured; Coculture Techniques; Deoxyuridine - pharmacology; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - therapy; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Ethics; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fibroblasts; Glucose; Growth factors; Human Physiology; Insulin; Internal Medicine; Islets of Langerhans - metabolism; Islets of Langerhans Transplantation - methods; Islets of Langerhans Transplantation - trends; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred C57BL; Neural crest; Neural Crest - cytology; Pancreas; Proliferation; Stem cells; Transplants & implants; United States > US; Cell culture; Diabetes; Proliferation; Neural crest; Beta cell; Endocrinopathy; Cell proliferation; Stem cell; Diabetes mellitus; Langerhans islet; Rodentia; In vitro; Vertebrata; Mammalia; β Cell; Endocrine pancreas
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-012-2542-0

Aims/hypothesis
Efficient stimulation of cycling activity in cultured beta cells would allow the design of new strategies for cell therapy in diabetes. Neural crest stem cells (NCSCs) play a role in beta cell development and maturation and increase the beta cell number in co-transplants. The mechanism behind NCSC-induced beta cell proliferation and the functional capacity of the new beta cells is not known.
Methods
We developed a new in vitro co-culture system that enables the dissection of the elements that control the cellular interactions that lead to NCSC-dependent increase in islet beta cells.
Results
Mouse NCSCs were cultured in vitro, first in medium that stimulated their proliferation, then under conditions that supported their differentiation. When mouse islet cells were cultured together with the NCSCs, more than 35% of the beta cells showed cycle activity. This labelling index is more than tenfold higher than control islets cultured without NCSCs. Beta cells that proliferated under these culture conditions were fully glucose responsive in terms of insulin secretion. NCSCs also induced beta cell proliferation in islets isolated from 1-year-old mice, but not in dissociated islet cells isolated from human donor pancreas tissue. To stimulate beta cell proliferation, NCSCs need to be in intimate contact with the beta cells.
Conclusions/interpretation
Culture of islet cells in contact with NCSCs induces highly efficient beta cell proliferation. The reported culture system is an excellent platform for further dissection of the minimal set of factors needed to drive this process and explore its potential for translation to diabetes therapy.