Adipose Tissue Engineering Laboratory
Why do we want to grow vascularised adipose tissue?
Vascularized adipose tissue (fat) is the major component of the human breast. In women who have had a mastectomy, tissue engineering would seem to be the ideal way of growing a replacement breast using the patient’s own tissue and cells. This form of breast reconstruction is likely to overcome the disadvantages of silicone or saline breast implants. This tissue could also be used to overcome contour defects resulting from the surgical excision of head and neck tumours.
How do we grow vascularised adipose tissue?
We have developed experimental models for growing new tissue in mice, rats, rabbits and pigs. The tissue grows spontaneously inside a plastic chamber which has been fitted with a local blood supply that is continuous with the body’s own blood supply, a biodegradable matrix scaffold (eg. Matrigel, a mouse tumour product matrix), cells of a particular tissue type (fat, muscle, bone marrow stem cells, etc) and specific growth or differentiation factors (eg. basic fibroblast growth factor). This “construct” is incubated under the skin. After 4 to 8 weeks the chamber fills with new adipose tissue (see picture on the right), which can be contoured to a desired shape (eg. breast). The future aim is to reproduce this vascularized fat generation to other mammalian species including humans.
New extracelluar matrices to support the growth of adipose tissue
Some of our experimental models use an extracellular matrix inside the chamber to help support the growth and development of the new tissue into vascularised fat. We aim to develop new matrices that can replace Matrigel and can grow tissue in species other than mice, with the eventual aim of scaling up to humans. One new extracellular matrix is Myogel TM a novel extracllular matrix that can be extracted from the skeletal muscles of species used in tissue engineering models including humnas. It contains grow factors as well as collagen and laminin and has supported tissue growth and cell differentiation both in vivo and in vitro. We have also added growth factors to gelatin beads to alter the speed of release and suspended them in collagen gel in chambers. We are also investigating synthetic matrices in collaboration with the Department of Chemical engineering at the University of Melbourne.
Stem cell seeding of vascularised chambers to produce adipose tissue
Precursor cells from the bone marrow are pluripotent, i.e. have the potential to develop into several tissues, eg. skin, muscle, bone, fat, etc. A combination of local environment and chemical factors decide their destiny. With the assistance of Assoc Prof Paul Simmons and his team at Peter MacCallum Cancer Institute, we harvested bone marrow cells from immature rats, sorted them, then expanded the resultant cells. The availability of adult stem cells opens the door to a future in which a patient’s stem cells can be harvested, then encouraged to proliferate and differentiate down any particular cell line to replace adipose or other tissue that may have been lost to tumour resection, trauma or deformity.
How do you grow larger amounts of adipose tissue in larger animals?
Using new designs of polymer sponges tailored to fit larger chambers (1.8 ml), both manufactured by colleagues at the Dept of Chemical Engineering, University of Melbourne, we grew 3-4 times the amount of tissue found in the standard chambers.
Similar experiments have now been performed in the pig. Using the breast region of the pig, a vascular bundle and its associated fat (~5 ml volume) was inserted into a perforated chamber (~78 ml volume) and the whole construct inserted beneath the skin for 6 weeks. At the time of harvest the chamber was full of vascularized tissue, mostly adipose tissue. Sufficient tissue to grow an average-sized breast was produced by this technique!
The next stage of these experiments is to optimize tissue production in pigs and eventually in humans, to show that larger blood vessels have the potential to produce a proportionally larger amount of new tissue. To this end we are now generating biologically compatible chemical additives (eg. scaffold materials, growth factors, etc) from the pig and human to minimize the immunological rejection of components added to the vascularized chamber constructs.