The Role of Chemically Modified Heparins on Embryonic Stem Cell Fate

Abstract

Embryonic stem cells have therapeutic potential in the treatment of different medical conditions, for example, tissue regeneration and wound repair. Current challenges affecting its clinical application include maintenance of pluripotency and directing lineage-specific differentiation. In that context, the extracellular matrix in the stem cell niche has been suggested to play an important role. Notably, the heparan sulfate proteoglycans (HSPGs) have been demonstrated to interact with and potentiate the effects of many classes of growth factors, including the family of FGFs. We have used selectively chemically modified heparins with different sulfation patterns as models of HS structure variations. Here we investigated their effects on mouse embryonic stem cells in terms of their lineage commitment. Broad structure-dependent effects on mouse ESC were noted on a range of markers of different lineage differentiation markers (by RT-PCR, and qPCR), and on various signalling pathway regulation (using Path scan signalling arrays). Using Western blotting, we also observed structure dependent effects in neural differentiation assays, through influencing FGF signalling via Erk phosphorylation. receptor tyrosine kinases phosphorylation arrays added an extra evidence on the structure-dependent effects. Overall, we have discovered that HS structures can be used to modulate signalling pathways in mouse ESCs, leading to changes in lineage commitment of pluripotent cells. Such compounds have the potential for extensive exploitation in control of pluripotency and lineage differentiation of stem cells in biotechnology applications.