Type

Journal Article

Authors

Garry P Duffy
Mary J. Murphy
Fergal J O'Brien
Helena M. Kelly
Conn L. Hastings
Frank P Barry

Subjects

Biochemistry

Topics
human mesenchymal stem cells chitosan cytology cells cultured drug effects therapy angiogenesis inducing agents delayed action preparations humans extremities blood supply pro angiogenic cell movement chemistry deferoxamine beta glycerophosphoric acid administration dosage metabolism hydrogel pharmacology hmsc desferrioxamine human umbilical vein endothelial cells ischemia neovascularization physiologic thermoresponsive hypoxia inducible factor 1 alpha subunit rheology glycerophosphates mesenchymal stromal cells cell proliferation

Development of a thermoresponsive chitosan gel combined with human mesenchymal stem cells and desferrioxamine as a multimodal pro-angiogenic therapeutic for the treatment of critical limb ischaemia (2012)

Abstract Critical limb ischaemia (CLI) is a debilitating ischaemic disease caused by vascular occlusion. Pro-angiogenic therapeutics have the potential to produce collateral vasculature, delaying or negating the need for amputation or invasive revascularisation. Thermoresponsive hydrogels can provide an in situ depot for the sustained release of drugs and provide protection and cohesion for encapsulated cells. Human mesenchymal stem cells (hMSCs) have demonstrated strong angiogenic potential in vitro and angiogenic efficacy in vivo. Desferrioxamine (DFO), a pharmacological activator of the pro-angiogenic hypoxia inducible factor-1α pathway, has shown pro-angiogenic efficacy in vivo. This study combined hMSCs and DFO with a thermoresponsive chitosan/β-glycerophosphate (β-GP) gel, to function as an injectable, multimodal, pro-angiogenic therapeutic for the treatment of CLI. This gel underwent a thermogelation beginning at 33 °C, and provided a sustained, biologically active release of DFO over the space of seven days, whilst permitting the survival, proliferation and migration of encapsulated hMSCs. hMSCs encapsulated in gel containing a 100 μM concentration of DFO displayed an upregulation in VEGF expression. The combination of hMSCs and DFO within the gel resulted in a synergistic enhancement in bioactivity, as measured by increased VEGF expression in gel-exposed human umbilical vein endothelial cells. This formulation displays significant potential as an injectable pro-angiogenic therapeutic for the treatment of CLI.
Collections Ireland -> University College Dublin -> Systems Biology Ireland
Ireland -> University College Dublin -> Institutes and Centres
Ireland -> University College Dublin -> Conway Institute Research Collection
Ireland -> University College Dublin -> SBI Research Collection
Ireland -> University College Dublin -> Conway Institute

Full list of authors on original publication

Garry P Duffy, Mary J. Murphy, Fergal J O'Brien, Helena M. Kelly, Conn L. Hastings, Frank P Barry

Experts in our system

1
Garry P Duffy
Royal College of Surgeons in Ireland
Total Publications: 54
 
2
Mary Murphy
National University of Ireland Galway
Total Publications: 20
 
3
Fergal J O'Brien
Royal College of Surgeons in Ireland
Total Publications: 265
 
4
Helena M Kelly
Royal College of Surgeons in Ireland
 
5
Conn L Hastings
Royal College of Surgeons in Ireland
Total Publications: 11
 
6
Frank Barry
National University of Ireland Galway
Total Publications: 47