Zahra Azizi
β-MSCs: Successful fusion of MSCs with β-cells results in a β-cell like phenotype
Azizi, Zahra; Lange, Claudia; Paroni, Federico; Ardestani, Amin; Meyer, Anke; Wu, Yonghua; Zander, Axel R.; Westenfelder, Christof; Maedler, Kathrin
Authors
Claudia Lange
Federico Paroni
Dr Amin Ardestani A.Ardestani@hull.ac.uk
Senior Lecturer
Anke Meyer
Yonghua Wu
Axel R. Zander
Christof Westenfelder
Kathrin Maedler
Abstract
Bone marrow mesenchymal stromal cells (MSC) have anti-inflammatory, antiapoptotic and immunosuppressive properties and are a potent source for cell therapy. Cell fusion has been proposed for rapid generation of functional new reprogrammed cells. In this study, we aimed to establish a fusion protocol of bone marrow-derived human MSCs with the rat beta-cell line (INS-1E) as well as human isolated pancreatic islets in order to generate insulin producing beta-MSCs as a cell-based treatment for diabetes. Human eGFP+ puromycin+ MSCs were co-cultured with either stably mCherryexpressing rat INS-1E cells or human dispersed islet cells and treated with phytohemagglutinin (PHA-P) and polyethylene glycol (PEG) to induce fusion. MSCs and fused cells were selected by puromycin treatment. With an improved fusion protocol, 29.8 ± 2.9% of all MSCs were β-MSC heterokaryons based on double positivity for mCherry and eGFP. After fusion and puromycin selection, human NKX6.1 and insulin as well as rat Neurod1, Nkx2.2, MafA, Pdx1 and Ins1 mRNA were highly elevated in fused human MSC/INS-1E cells, compared to the mixed control population. Such induction of betacell markers was confirmed in fused human MSC/human dispersed islet cells, which showed elevated NEUROD1, NKX2.2, MAFA, PDX1 and insulin mRNA compared to the mixed control. Fused cells had higher insulin content and improved insulin secretion compared to the mixed control and insulin positive beta-MSCs also expressed nuclear PDX1. We established a protocol for fusion of human MSCs and beta cells, which resulted in a beta cell like phenotype. This could be a novel tool for cell-based therapies of diabetes.
Citation
Azizi, Z., Lange, C., Paroni, F., Ardestani, A., Meyer, A., Wu, Y., …Maedler, K. (2016). β-MSCs: Successful fusion of MSCs with β-cells results in a β-cell like phenotype. Oncotarget, 7(31), 48963-48977. https://doi.org/10.18632/oncotarget.10214
Journal Article Type | Article |
---|---|
Acceptance Date | Apr 19, 2016 |
Online Publication Date | Jun 21, 2016 |
Publication Date | Aug 2, 2016 |
Deposit Date | Jan 4, 2024 |
Publicly Available Date | Jan 8, 2024 |
Journal | Oncotarget |
Print ISSN | 1949-2553 |
Electronic ISSN | 1949-2553 |
Publisher | Impact Journals |
Peer Reviewed | Peer Reviewed |
Volume | 7 |
Issue | 31 |
Pages | 48963-48977 |
DOI | https://doi.org/10.18632/oncotarget.10214 |
Keywords | MSCs; Cell fusion; Beta-cells; Islets; Diabetes; Pathology Section |
Public URL | https://hull-repository.worktribe.com/output/4461703 |
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Copyright Statement
Creative Commons Licence: Attribution 4.0 International License. See: https://creativecommons.org/licenses/by/4.0/
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