Type

Journal Article

Authors

Garry P Duffy
Fergal J O'Brien
Frank P. Barry
Conn L. Hastings
Mary J Murphy
Kevin McSorley
Timothy O'Brien
Erica G Tierney
Sally-Ann Cryan

Subjects

Biochemistry

Topics
cells cultured mesenchymal stromal cells peptides gene activated matrices gene transfer ephb4 cells mesenchymal stem cells genetic therapy humans receptor dna cultured proto oncogene proteins c akt ephrinb2 scaffold bone regeneration cell differentiation green fluorescent proteins anatomy ephrin b2 plasmids non viral vector osteogenesis polyethyleneimine receptor ephb4 tissue scaffolds

High levels of ephrinB2 over-expression increases the osteogenic differentiation of human mesenchymal stem cells and promotes enhanced cell mediated mineralisation in a polyethyleneimine-ephrinB2 gene-activated matrix (2013)

Abstract Gene therapy can be combined with tissue engineering constructs to produce gene-activated matrices (GAMs) with enhanced capacity for repair. Polyethyleneimine (PEI), a non-viral vector, has previously been optimised for high efficiency gene transfer in rat mesenchymal stem cells (rMSCs). The use of PEI to transfect human MSCs (hMSCs) with ephrinB2 is assessed here. Recently a role for the ephrinB2 ligand and EphB4 receptor duo has been proposed in bone remodelling. Herein, over-expression of the ephrinB2 ligand resulted in increased osteogenic differentiation in hMSCs. As ephrinB2 is a cell surface anchored ligand which only interacts with cells expressing the cognate EphB4 receptor through direct contact, we have shown that direct cell–cell contact between two neighbouring cells is responsible for enhanced osteogenesis. In an effort to begin to elucidate the molecular mechanisms at play downstream of ephrinB2 over-expression, RT-PCR was performed on the GAMs which revealed no significant changes in runx2 or BMP2 expression but an upregulation of osterix (Osx) and Dlx5 expression prompting the belief that the mode of osteogenesis is independent of the BMP2 pathway. This select interaction, coupled with the transient gene expression profile of PEI, makes the PEI-ephrinB2 GAM an ideal candidate matrix for a bone targeted GAM.
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Full list of authors on original publication

Garry P Duffy, Fergal J O'Brien, Frank P. Barry, Conn L. Hastings, Mary J Murphy, Kevin McSorley, Timothy O'Brien, Erica G Tierney, Sally-Ann Cryan

Experts in our system

1
Garry P Duffy
Royal College of Surgeons in Ireland
Total Publications: 59
 
2
Fergal J O'Brien
Royal College of Surgeons in Ireland
Total Publications: 280
 
3
Frank Barry
National University of Ireland Galway
Total Publications: 48
 
4
Conn L Hastings
Royal College of Surgeons in Ireland
Total Publications: 11
 
5
Mary Murphy
National University of Ireland Galway
Total Publications: 24
 
6
Timothy O'Brien
National University of Ireland Galway
Total Publications: 35
 
7
Erica G Tierney
Royal College of Surgeons in Ireland
Total Publications: 9
 
8
Sally-Ann Cryan
Royal College of Surgeons in Ireland
Total Publications: 70