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Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuroanatomy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2012 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 7, 2016-2025 p.Article in journal (Refereed) Published
Abstract [en]


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.


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.


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.


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.

Place, publisher, year, edition, pages
2012. Vol. 55, no 7, 2016-2025 p.
Keyword [en]
Beta cell, Cell culture, Diabetes, Neural crest, Proliferation
National Category
Endocrinology and Diabetes
URN: urn:nbn:se:uu:diva-178542DOI: 10.1007/s00125-012-2542-0ISI: 000305215200020OAI: oai:DiVA.org:uu-178542DiVA: diva2:542428

De 2 förstaförfattarna delar förstaförfattarskapet

De 2 sistaförfattarna delar sistaförfattarskapet

Available from: 2012-08-01 Created: 2012-07-31 Last updated: 2015-01-23Bibliographically approved
In thesis
1. The beneficial Effects of Neural Crest Stem Cells on Pancreatic      β–cells
Open this publication in new window or tab >>The beneficial Effects of Neural Crest Stem Cells on Pancreatic      β–cells
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with type-1 diabetes lose their β-cells after autoimmune attack. Islet transplantation is a co-option for curing this disease, but survival of transplanted islets is poor. Thus, methods to enhance β-cell viability and function as well as methods to expand β-cell mass are required. The work presented in this thesis aimed to study the roles of neural crest stem cells or their derivatives in supporting β-cell proliferation, function, and survival.

In co-culture when mouse boundary cap neural crest stem cells (bNCSCs) and pancreatic islets were in direct contact, differentiating bNCSCs strongly induced β-cell proliferation, and these proliferating β-cells were glucose responsive in terms of insulin secretion. Moreover, co-culture of murine bNCSCs with β-cell lines RIN5AH and β-TC6 showed partial protection of β-cells against cytokine-induced β-cell death. Direct contacts between bNCSCs and β-cells increased β-cell viability, and led to cadherin and β-catenin accumulations at the bNCSC/β-cell junctions. We proposed that cadherin junctions supported signals which promoted β-cell survival. We further revealed that murine neural crest stem cells harvested from hair follicles were unable to induce β-cell proliferation, and did not form cadherin junctions when cultured with pancreatic islets. Finally, we discovered that the presence of bNCSCs in co-culture counteracted cytokine-mediated insulin-producing human EndoC-βH1 cell death. Furthermore, these two cell types formed N-cadherin, but not E-cadherin, junctions when they were in direct contact. In conclusion, the results of these studies illustrate how neural crest stem cells influence β-cell proliferation, function, and survival which may improve islet transplantation outcome.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 67 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1037
Neural Crest Stem Cells, Pancreatic Islets, β-cell proliferation, β-cell survival, Cadherin
National Category
Research subject
Medical Science
urn:nbn:se:uu:diva-233157 (URN)978-91-554-9056-0 (ISBN)
Public defence
2014-11-18, B/B7:113a, Biomedical center, Husargatan 3, Uppsala, 13:15 (English)
Available from: 2014-10-27 Created: 2014-09-29 Last updated: 2015-01-23

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Vasylovska, SvitlanaOlerud, JohanNgamjariyawat, AnongnadJansson, LeifKozlova, Elena N.
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NeuroanatomyDepartment of NeuroscienceDepartment of Medical Cell Biology
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