General Monthly Meeting
Skin Deep
Phil Moore, Director, Skin Technologies Research Centre
School of Science Food and Horticulture, University of Western
Sydney.
Date: Wednesday, 4th September, 2002
Time: 6:00 for 6:30 pm
Venue: Search & Discover Room, Australian Museum,
Collins St., Sydney (William St. entrance)
It has been said that Brutus was no more than a resounding set of vocal cords wrapped up in skin. Whilst some might consider that there are better and more recent examples, to most people this would seem a somewhat economical definition of our most visible organ. Nevertheless, apart from its decorative possibilities, skin is still generally regarded as a more-or-less loose body wrapping that protects the important bits inside from drying out.
In fact, skin has other valuable attributes. It is certainly the largest organ of the body, and unlike most internal items, all of it needs to be intact to function normally. Those of us unfortunate enough to suffer from skin diseases, burns or ulcerations, can be at particular risk if affected areas of skin do not heal. In many cases, this may be a slow, difficult and invariably painful process, requiring removal of skin from uninvolved areas of the body and grafting them to the wound site.
Fifteen years ago, an artificial skin was generated in the lab. This was a major advance and gave hope to patients requiring skin grafts. The artificial skin was composed of cultured skin cells embedded in a collagen matrix and thus had many of the properties of the natural item. Furthermore, the fact that the artificial skin could be made up of the patient's own skin cells, minimised the risk of graft rejection. The potential of this cultured construct as a skin substitute for grafting was immediately apparent.
Artificial skin was also part of a new wave of research into tissue engineering: the generation of new organs in the laboratory. Thus, in addition to the possibility of replacing damaged or genetically-deficient skin with a cultured substitute, there was now the possibility of using skin as a vehicle for delivering biologically active compounds to the body. The thinking was that the activities of organs that were not functioning correctly or had lost their efficacy could be augmented or replaced with an engineered skin graft. One simple approach was to identify diseases caused by loss of function of a single gene, insert that gene into skin cells in culture and reconstruct an artificial skin for grafting. Another was the delivery of therapeutic agents. Upon grafting, the skin becomes a bioreactor, delivering the product of the introduced gene to the host. Gene therapy is here.
From 1970 to 74, Phil Moore held Postdoctoral Fellowships at the Institute of Animal Genetics, Edinburgh, the Institut de Biologie Moleculaire, Faculty of Sciences of Paris, the Medical Nobel Institute, Karolinska Institutet, Stockholm, and the Finsen Radiation Institute, Copenhagen. Studies of changes in gene activity of cells undergoing terminal differentiation and reactivation were supported by the Ford Foundation, EMBO and the Wellcome Trust. In 1974 through 76, he was Queen Elizabeth II Fellow at the ANU, Canberra. He spent the next three years as Lecturer at the School of Biological Sciences, Macquarie University. In 1979 he was Senior Principal Research Scientist at the CSIRO Division of Animal Production until its closure in 2000, research centred on the regulation of hair follicle development and growth in mammals. During this time, an international patent was awarded to Moore and colleagues for an invention based on observations of the responses of wool and hair follicles to epidermal growth factor. In 1984 he was AAS-Weizmann Fund Fellow at the Weizmann Institute, Rehovot. He was a Member of the editorial board of the international journal Anticancer Research from 1988 to 92. In 1993 he was Research Professor at the School of Science, Food and Horticulture, University of Western Sydney. Research areas include mechanisms of pattern and morphogenesis in skin, autocrine growth pathways in pigment cells, growth factors and inductive tissue interactions and the applications of cultured skin to gene therapeutic approaches to disease.
by Karina Kelly.
Prof. Phillip Moore from the University of Western Sydney addressed the Society on the subject of skin. His entertaining talk entitled Skin Deep was all about skin and hair follicles. Prof. Moore touched on the impact of gene technology on skin research then moved to skin and hair. We learned that you are born with all the skin follicles you will ever have and that humans have on average 4 - 5 hair follicles per square mm while sheep have 100.
We learned that hair growth products for balding men is a multi billion dollar industry yet almost all of these products don't work.
The skin is made of an epidermal and a dermal layer. Hair follicles form in humans at 3 months gestation. A "plug" of dermal and epidermal cells forms into a hair follicle. Inside the follicle are the most rapidly dividing cells of the body which produce hair, made of keratin. Prof. Moore explained that in theory it is possible to take the "dermal papilla" cells out of the skin in order to make new follicles. Research on this area of hair loss treatment is underway.
There are different kinds of follicles, which produce different kinds of hair. Fine merino wool, for instance, is produced from branched follicles.
Prof. Moore discovered in his work at the CSIRO that epidermal growth factors inhibited hair growth when administered to mice. He treated sheep with the same mouse epidermal growth factor and five days later their wool fell out. This research was then funded by the Wool Corp who were trying to find a new way to shear sheep at a time when there was a great deal of tension between the shearers and farmers. Moore continued this work at CSIRO's Division of Animal Production while in WA, work continued on a robot shearer which was ultimately unsuccessful.
The growth factor came from the mouth salivary gland of mice and there simply were not enough mice to make the factor. The small protein had not been described and so the gene was sequenced and this sequence was inserted via a plasmid into bacteria. The bacteria could them produce large quantities of EGF (epidermal growth factor).
While a sheep produces wool to the value of $10 per kg, angora rabbit wool is worth $100 per kg and they are much harder to shear. Moore applied his technology to the angoras and it worked but the business he was dealing with went broke. He is now working with a new business in NSW, which is being set up using French angora rabbits.
Moore has also done research into other areas of skin. Firstly into melanoma by trying to produce a transgenic mouse which would model human melanoma. This was unsuccessful as mice simply don't suffer from melanoma.
He also looked at the possibility of skin as a method of delivering gene therapy by putting the gene into skin cells, growing them up and then grafting them onto the sufferer.
He successfully put the insulin gene (from beta cells in the pancreas) into a retroviral vector and then into skin cells. In this way he was able to graft the skin onto diabetic mice and bring their blood glucose back to normal.
Prof. Moore has most recently been working on artificial skin for grafting onto burn patients. While the most effective solution would be to grow the patients' own cells, this would take weeks - too long for someone suffering severe burns. So he's now working with a large international company, Ortec, on an "artificial" skin that can provide a safe covering which allows the patient's own skin to grow back with minimal scarring. The artificial skin does not have hair follicles or glands and therefore cannot "breathe" like real skin.
Professor Moore's fascinating journey into "our largest organ" was accompanied by many interesting images, which made us wonder at the complexity and flexibility of skin. Many questions followed it, and Karina Kelly then thanked the speaker.