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Vascular biology

Research in the Vascular Biology Group focuses on creating micro-vascular (capillary) blood vessel networks for tissue regeneration, both in tissue engineering of new organs or tissues, or as part of a wound healing response. The group’s work originally focused on the spontaneous formation of capillary networks that sprout from large blood vessels isolated in a tissue engineering chamber in an animal. This chamber model has grown cardiac muscle, fat, pancreatic islets and liver tissue.  More recently the group has focused on growing capillary networks in the laboratory to vascularize 3D tissue engineering constructs prior to implantation in an animal model.

Research overview

A major problem in assembling 3-dimensional tissue engineering constructs (support materials and organ/tissue specific cells) is providing an interconnected blood vessel network (vascularization) throughout the construct that can immediately supply blood to all cells in the construct. Traditional vascularization techniques take at least a week and many construct cells die during this time.   A solution is to pre-vascularize the tissue engineering construct in the laboratory prior to implantation in an animal model. The Vascular Biology Group’s current projects focus on the technique of pre-vasculariation of porous scaffolds that can be implanted in wounds, and pre-vascularization of small organ-like structures called organoids, all in the laboratory. We are also investigating various ways to implant the main cell type that forms capillaries - endothelial cells in multi-cellular spheroids. Most of our current research involves human tissue sand cells.

Research Themes

Pre-vascularization of porous scaffolds for wound healing

The aim of this study is to form human capillary networks from human endothelial cells and transplant into animal wound models. This project aims to increase vascularization in difficult to heal wounds.   Staff member involved: Dr Anne Kong.

Relevant Publications:
Chan EC, Kuo S-M, Kong AM, Morrison WA, Dusting GJ, Mitchell GM, Lim SY,  Liu G-S.  2016, Three dimensional collagen scaffold promotes intrinsic vascularisation for tissue engineering applications.  PLoS One. 2016 Feb 22;11(2):e01497992.

Human blood vascular capillaries derived from endothelial cell spheroids

Implantation of cells in animal models is usually completed by implanting a large number of cells in fluid called a single cell suspension. However it has been observed by our group and others that many cells die as a result of this process. Multicellular spheroids are reported to demonstrate improved survival and function in vivo.  We have been investigating the capillary forming capabilities of human endothelial cells as multicellular spheroids in laboratory assessments and in animal models. PhD student Mr Kam Truong is completing this project.

Relevant Publications:
Mitchell GM, Morrison WA. In vivo vascularization for large volume soft tissue engineering, In (Ed) Brey EM: Vascularization: Regenerative Medicine and Tissue Engineering, CRC Press, 2014, Chapter 17, Pages 34
Tilkorn D, Bedogni A, Keramidaris E, Han X, Palmer J, Dingle AM, Cowling BS, Williams MD, Mc Kay SM, Pepe L, Deftereos A, Morrison WA, Penington A, Mitchell GM.  Implanted myoblast survival is dependent on the degree of vascularization in a novel delayed implantation /prevascularization tissue engineering model.    Tissue Eng Part A. 2010 Jan;16(1):165-78.3-362.

Creating a human liver organoid to treat liver disease

The project aims to assemble human liver organoids from liver progenitor cells, liver endothelial cells and mesenchymal stem cells. The cells are isolated from human liver and fat tissues available from discarded tissues at operation.   In parallel we are also deriving these cells from human adult stem cells and also forming human liver-like organoids. All organoids are formed in the laboratory, with the aim of using them in animal models of liver disease. PhD student Dr Kiryu Yap is completing this project.  

We also have a mouse liver tissue engineering project being completed by Research Assistant: Ms Yi-wen Gerrand and Dr Kiryu Yap.

Relevant Publications:
Forster NA, Palmer JA, Yeoh GC, Ong W-C, Mitchell GM, Slavin J, Tirnitz-Parker J, Morrison WA, Expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice. Tissue Engineering Part C, 2011 Mar;17(3):359-66.
Yap KK,  Dingle AM,  Palmer JA,  Dhillon R, Lokmic Z,  Penington AJ, Yeoh GC, Morrison WA,  Mitchell GM, Enhanced liver progenitor cell survival and differentiation in vivo by spheroid implantation in a vascularized tissue engineering chamber, Biomaterials. 2013 May;34(16):3992-4001.

Student Projects

Staff

  • A/Prof Geraldine Mitchell
  • Dr Anne Kong
  • Yi-wen Gerrand
  • Dr Kiryu Yap, PhD student
  • Mr Kam Truong, PhD student
  • Dr Susana Benitez, Visiting Fellow

Publication Highlights

  1. Taylor CJ, Church JE, Williams MD, Gerrand YW, Keramidaris E, Palmer JA,  Galea LA, Penington AJ, Morrison WA, and  Mitchell GM.  Hypoxic preconditioning of myoblasts implanted in a tissue engineering chamber significantly increases local angiogenesis via upregulation of myoblast VEGF-A expression, and downregulation of miRNA-1, miRNA-206 and Angiopoietin 1.  Journal of Tissue Engineering and Regenerative  Medicine, 2018 Jan;12(1):e408-e421.
  2. Dingle AM*, Yap KK*, Gerrand Y-W, Taylor CJ, Keramidaris E,  Lokmic Z,  Kong AM, Peters HL, Morrison WA and Mitchell GM.  Characterization of isolated liver sinusoidal endothelial cells for liver bio-engineering. Angiogenesis, 2018, 21(3), 581-597.  *joint first authors.
  3. Yap KK, Yeoh GC, Morrison WA, Mitchell GM. The vascularised chamber as an in vivo bioreactor. Trends in Biotechnology,  2018 Oct;36(10):1011-1024.