Creating transplantable human capillary networks derived from adult human stem cells

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Project Status
Future
Department
Surgery
Location
St Vincent's Hospital
Supervisor Email Number Webpage
A/Prof Geraldine Mitchell Personal web page

Project Details

A major issue in chronic skin wounds is the growth of blood vessels (revascularization) into the wound site. Although commercially available dermal matrices in combination with skin grafts can create skin coverage, the revascularization of complicated wounds is often difficult. In the Vascular Biology Group we are looking at a number of techniques to boost the vascularization of wounds.  

Pre-vascularization of a porous dermal matrix in the cell culture laboratory can be achieved by seeding human endothelial cells into the scaffold which will form an interconnected capillary network within 24 hours. When implanted into a wound, the pre-vascularized scaffold would bring an additional capillary network into ischemic chronic wounds. In this project human endothelial cells derived from induced pluripotent stem cells (iPSC) are seeded into a porous dermal matrix (a polyurethane scaffold currently in clinical trials will be used). iPSC have the advantage that they are patient derived and many millions of patient–specific  endothelial cells can be generated.  An additional material (human fibrin) that can penetrate the pores of the dermal matrix will also support the endothelial cells. In culture the most favorable conditions that promote capillary tube formation within the scaffold will be determined, using human compatible products. Additional iPSC derived vascular support cells such as vascular smooth muscle cells and pericytes will be co-cultured with the endothelial cells to accelerate capillary network maturity.

In a second phase of the project the pre-vascularized scaffold (with human iPSC capillaries incorporated) will be transplanted into a wound in the ‘nude’ (immunosuppressed) rat back. We anticipate that the human capillaries will inosculate (join) with adjacent rat capillaries and become functional – that is carry rat blood throughout the scaffold – this will be monitored morphologically and morphometrically and via fluorescent microscopy tracking of labelled implanted cells, and via vascular perfusions.

This project is conducted in St Vincent’s Institute of Medical Research, Vascular Biology Group (O’Brien Institute Department of SVI).


School Research Themes

Cardiometabolic



Research Opportunities

PhD, Masters by Research, Honours, Master of Biomedical Science
Graduate Research Students who are interested in joining this project will need to consider their elegibility as well as other Graduate Research requirements before contacting the supervisor of this research

View application process

Key Contact

For further information about this research, please contact a supervisor.

Department

Surgery

Research Node

St Vincent's Hospital