Chorionic and amniotic placental membrane-derived stem cells, from gestational diabetic women, have distinct insulin secreting cell differentiation capacities
Liyun Chen
School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
Search for more papers by this authorCorresponding Author
Nicholas R. Forsyth
School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.
Correspondence
Nicholas R. Forsyth, School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Thornburrow Drive, Stoke-on-Trent, U.K.
Email: [email protected]
Search for more papers by this authorPensee Wu
School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.
Academic Unit of Obstetrics and Gynaecology, University Hospital of North Midlands Stoke-on-Trent, U.K.
Keele Cardiovascular Research Group, Institute for Applied Clinical Sciences and Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University Stoke-on-Trent, U.K.
Search for more papers by this authorLiyun Chen
School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
Search for more papers by this authorCorresponding Author
Nicholas R. Forsyth
School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.
Correspondence
Nicholas R. Forsyth, School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Thornburrow Drive, Stoke-on-Trent, U.K.
Email: [email protected]
Search for more papers by this authorPensee Wu
School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.
Academic Unit of Obstetrics and Gynaecology, University Hospital of North Midlands Stoke-on-Trent, U.K.
Keele Cardiovascular Research Group, Institute for Applied Clinical Sciences and Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University Stoke-on-Trent, U.K.
Search for more papers by this authorAbstract
Women with gestational diabetes mellitus (GDM), and their offspring, are at high risk of developing type 2 diabetes. Chorionic (CMSCs) and amniotic mesenchymal stem cells (AMSCs) derived from placental membranes provide a source of autologous stem cells for potential diabetes therapy. We established an approach for the CMSC/AMSC-based generation of functional insulin-producing cells (IPCs). CMSCs/AMSCs displayed significantly elevated levels of NANOG and OCT4 versus bone marrow-derived MSCs, indicating a potentially broad differentiation capacity. Exposure of Healthy- and GDM-CMSCs/AMSCs to long-term high-glucose culture resulted in significant declines in viability accompanied by elevation, markedly so in GDM-CMSCs/AMSCs, of senescence/stress markers. Short-term high-glucose culture promoted pancreatic transcription factor expression when coupled to a 16-day step-wise differentiation protocol; activin A, retinoic acid, epidermal growth factor, glucagon-like peptide-1 and other chemical components, generated functional IPCs from both Healthy- and GDM-CMSCs. Healthy-/GDM-AMSCs displayed betacellulin-sensitive insulin expression, which was not secreted upon glucose challenge. The pathophysiological state accompanying GDM may cause irreversible impairment to endogenous AMSCs; however, GDM-CMSCs possess comparable therapeutic potential with Healthy-CMSCs and can be effectively reprogrammed into insulin-secreting cells.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| term2988-supp-0001-Figure_S1.tifTIFF image, 1.1 MB | Figure S1. The staining of senescence-associated-beta-galactosidase (SA-β-Gal) activity in HG and LG culture. The effect of HG on cellular senescence was measured by SA-β-Gal activity. In H-/G- CMSCs, no cellular senescence was detected in LG culture during a 30-day period. In H-/G-AMSCs, senescence was detected in both LG and HG culture. Significantly increased SA-β-Gal activity was observed in LG-D30 vs LG-D10 in both H-AMSCs and G-AMSCs. |
| term2988-supp-0002-Figure_S2.tifTIFF image, 398.5 KB | Figure S2. The cell growth, senescence, and cell death in HG culture. To eliminate the possibility that cell senescence and death observed in HG culture was the result of cell over-confluence, cells seeded at the number of 1x105 on day 0, passaged and reseeded at the same number on day 10 and 20. The increase of cell numbers was examined by cell count, cell viability and senescence on day 10, 20, 30 were determined by calcein-AM/EthD-1 and SA-β-Gal activity, respectively. (a) The proliferation of H-/G-CMSCs/AMSCs was reduced in day10-20 and day20-30 compared day0-10. (b) Cell senescence was increased in H-/G- CMSCs and AMSCs while G-CMSCs/AMSCs showed higher increasing rate than H-CMSCs/AMSCs. (c) Cell viability was decreased in H-/G-CMSCs/AMSCs under HG culture. Data are shown mean ± SD from 3 independent experiment. |
| term2988-supp-0003-Figure_S3.tifTIFF image, 1.2 MB | Figure S3. Immunofluorescent staining of insulin and PDX-1 coexpression. Confocal images of H-/G- CMSCs and AMSCs derived IPCs showed coexpression of insulin (red) and PDX1 (green). DAPI was used as nuclear counterstain in blue. (scale bar, 100 μm). Undifferentiated H-/G- CMSCs and ASMCs staining image of insulin and PDX-1 expression showed at the bottom left corner. |
| term2988-supp-0004-Figure_S4.tifTIFF image, 360.2 KB | Figure S4. The co-localisation of insulin and glucagon analysed by Pearson correlation coefficient (r). The r value calculated by Image J Coloc2 plugin, ranges from +1 (perfect correlation) to -1 (anti-correlation) and 0 indicates no correlation. |
| term2988-supp-0005-Table_S1-S3.docxWord 2007 document , 14.6 KB |
Table S1. Minimal criteria for defining MSCs suggested by The International Society for Cellular Therapy Table S2. Primers used for real-time PCR Table S3. The expression of CD makers in H-/G- CMSCs/AMSCs |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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