CHARACTERIZATION AND DIFFERENTIATION OF PLACENTA-DERIVED MESENCHYMAL STEM CELLS FROM GDM WOMEN INTO INSULIN PRODUCING CELLS FOR PERSONALISED MEDICINE

Chen, Liyun; Merkhan, Marwan; Forsyth, Nicholas R.; Wu, Pensee

Abstract

Objectives: Chorionic and amniotic MSCs (CMSCs/AMSCs) are derived
from different sides of placental membrane. Women with a history of
gestational diabetes mellitus have a high risk of developing subsequent
diabetes. As cell therapy is a promising diabetes treatment, placental MSCs
can be a valuable autologous source. We aim to evaluate whether the
hyperglycaemic environment alters the biological properties of GDMMSCs and further to establish a feasible method for generating functional
insulin-producing cells (IPCs) for cell transplantation.

Methods: All placentas were collected from University Hospital of North
Midlands, UK. The characterization of MSCs was carried out by analysing
pluripotent gene, immunophenotyping, tri-lineages differentiation, coculturing with immune cells and cytokine analysis. We also investigated
the high glucose effect on CMSCs/AMSCs and trans-differentiated CMSCs/
AMSCs to IPCs by stimulating with various compounds. The efficiency was
examined by qPCR, immunostaining and ELISA.

Results: Placental membranes contain abundant MSCs which express
stemness markers. To characterise healthy and GDM MSCs, tri-lineage
differentiation and MSC phenotypical markers were investigated, where
GDM-MSCs demonstrated greater adipogenic tendency and a significant
increase in CD45. Moreover, the interaction between CMSCs/AMSCs and
immune cells showed that CMSCs possessed better immunosuppressive
capacity than AMSCs; however GDM environment altered the immunomodulatory ability in GDM-CMSCs/AMSCs. Finally, we found long-term high glucose culture induce CMSCs/AMSCs apoptosis and premature
senescence which caused greater effect on GDM-MSCs than healthy-MSCs.
On the other hand, short-term high glucose treatment induced b-cell
transcription factors expression and with sequential stimulation; we successfully generated IPCs from GDM and healthy CMSCs which secreted insulin upon glucose stimulation.

Conclusion: We highlight the importance of the maternal intrauterine
environment in altering the placental MSC biological properties and
develop a feasible approach for generating IPCs from GDM-MSCs. The finding could contribute to the future development of autologous cell therapy of using MSCs derived from GDM placenta.

Citation

Chen, L., Merkhan, M., Forsyth, N. R., & Wu, P. (2018, September). CHARACTERIZATION AND DIFFERENTIATION OF PLACENTA-DERIVED MESENCHYMAL STEM CELLS FROM GDM WOMEN INTO INSULIN PRODUCING CELLS FOR PERSONALISED MEDICINE. Poster presented at International Federation of Placenta Associations Meeting, Tokyo, Japan

• Presentation Conference Type: Poster
• Conference Name: International Federation of Placenta Associations Meeting
• Conference Location: Tokyo, Japan
• Start Date: Sep 21, 2018
• End Date: Sep 24, 2018
• Deposit Date: Jun 29, 2023