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Neural crest stem cells from hair follicles and boundary cap have different  effects on pancreatic islets in vitro
Laboratory of Cell Proliferation, Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology. (Regenerative Neurobiology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology. (Regenerative Neurobiology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology. (Regenerative Neurobiology)
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2015 (English)In: International Journal of Neuroscience, ISSN 0020-7454, E-ISSN 1563-5279, Vol. 125, no 7, 547-554 p.Article in journal (Refereed) Published
Abstract [en]

Purpose:

Neural crest stem cells derived from the boundary cap (bNCSCs), markedly promote survival, proliferation and function of insulin producing β-cells in vitro and in vivo after coculture/transplantation with pancreatic islets [ 1, 2 ]. Recently, we have shown that beneficial effects on β-cells require cadherin contacts between bNCSCs and β-cells [ 3, 4 ]. Here we investigated whether hair follicle (HF) NCSCs, a potential source for human allogeneic transplantation, exert similar positive effects on β-cells.

Materials and Methods:

We established cocultures of HF-NCSCs or bNCSCs from mice expressing enhanced green fluorescent protein together with pancreatic islets from DxRed expressing mice or NMRI mice and compared their migration towards islet cells and effect on proliferation of β-cells as well as intracellular relations between NCSCs and islets using qRT-PCR analysis and immunohistochemistry.

Results:

Whereas both types of NCSCs migrated extensively in the presence of islets, only bNCSCs demonstrated directed migration toward islets, induced β-cell proliferation and increased the presence of cadherin at the junctions between bNCSCs and β-cells. Even in direct contact between β-cells and HF-NCSCs, no cadherin expression was detected.

Conclusions:

These observations indicate that HF-NCSCs do not confer the same positive effect on β-cells as demonstrated for bNCSCs. Furthermore, these data suggest that induction of cadherin expression by HF-NCSCs may be useful for their ability to support β-cells in coculture and after transplantation.

Place, publisher, year, edition, pages
London: Informa Healthcare, 2015. Vol. 125, no 7, 547-554 p.
Keyword [en]
Diabetes, cell culture, coculture, intercellular contacts, migration
National Category
Neurosciences
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-233149DOI: 10.3109/00207454.2014.950373ISI: 000359884200011PubMedID: 25077520OAI: oai:DiVA.org:uu-233149DiVA: diva2:750717
Funder
Swedish Research Council, 20716
Note

De 2 första författarna delar förstaförfattarskapet

Available from: 2014-09-29 Created: 2014-09-29 Last updated: 2017-12-05
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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1037
Keyword
Neural Crest Stem Cells, Pancreatic Islets, β-cell proliferation, β-cell survival, Cadherin
National Category
Neurosciences
Research subject
Medical Science
Identifiers
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)
Opponent
Supervisors
Available from: 2014-10-27 Created: 2014-09-29 Last updated: 2015-01-23

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Publisher's full textPubMedhttp://informahealthcare.com/doi/abs/10.3109/00207454.2014.950373

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Ngamjariyawat, AnongnadVasylovska, SvitlanaKönig, NiclasTrolle, CarlLau, JoeyCarlsson, Per-OlaN. Kozlova, Elena

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Regenerative neurobiologyDepartment of Medical Cell Biology
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