Low Oxygen Tension Modulates the Insulin-like Growth Factor Signaling Via Insulin-like Growth Factor-I Receptor and Insulin Receptor to Maintain Stem Cell Identity in Placental Mesenchymal Stem Cells

Presentation Number: SUN-0640
Date of Presentation: June 22nd, 2014

Amer Youssef*1 and Victor Khin Han2
1Children's Health Research Institute - Western University, London, ON, Canada, 2Children's Hlth Rsrch Inst, London, ON, Canada


Placental mesenchymal stem cells (PMSCs) are readily available multipotent stem cells for use in regenerative therapies. The microenvironment of PMSCs is dynamic throughout gestation and determines changes in cell fate.  For optimal stem cell identity and fate manipulation, PMSCs must be maintained in culture conditions that mimic the in vivo microenvironment.  In vivo, PMSCs develop in low oxygen tension and varying insulin-like growth factor (IGF, IGF-I and IGF-II) concentration that increase gradually as pregnancy progresses. However, the signaling of IGF-I or IGF-II in low oxygen tension microenviroenment in stem cells is not well investigated. Therefore, we hypothesize that IGF-I and IGF-II signal via distinct signaling pathways to maintain PMSC multipotency under low oxygen tension. PMSCs from early human placentae were used to investigate the role of IGF-I and IGF-II on proliferation, multipotency and signaling through ERK1/2 and AKT pathways. we found that low oxygen tension enhanced the expression of IGF-II greater than IGF-I, which was reduced. IGF-I simulated higher phosphorylation of IGF-IRβ, ERK1/2 and AKT that were reduced in low oxygen tension. Proliferation was increased by IGFs and was enhanced further by low oxygen tension. Neutralization of IGF-IR inhibited PMSC proliferation in room air, whereas in low oxygen tension, PMSCs utilized IR to mediate IGF actions. We observed that low oxygen tension increased IR expression level. We conclude that maintaining PMSCs under low oxygen tension and appropriate IGF concentrations will maintain stem cell characteristics in vitro, that are mediated cooperatively between the IGF-IR and the IR. Therefore, understanding the in vivo microenvironment of stem cells can improve their use for in vitro application in tissue regenration therapy.


Nothing to Disclose: AY, VKH