The influence of cortisone and implantation site on bone and cartilage induction in various animals.

When decalcified lyophilised bone matrix (Urist, Silverman, Biiring, Dubuc and Rosenberg 1967) is implanted intramuscularly in other animals of the same species, new cartilage, bone and bone marrow appear. The sequence of events leading to this induction and its main features were described in detail by Urist and his co-workers (Urist and Dowell 1968; Urist, Dowell, Hay and Strates 1968: Thompson and Urist 1970). Their view was that after partial resorption of the implanted matrix, endomysial cells dedifferentiated, multiplied and then differentiated into chondroblasts or osteoblasts (Urist 1970). Recently a further technique for cartilage and bone induction has been described, entailing the use of living cells (Anderson, Merker and Fogh 1964: Wlodarski 1969: Wlodarski, Hinek and Ostrowski 1970). When established tissue culture lines of epithelial cells of both normal and neoplastic origin are grafted intramuscularly, bone and cartilage develop in the adjacent host tissue (Wlodarski 1969, Wbodarski and colleagues 1970). This phenomenon occurs in transplants between animals of different species, though an immunosuppressant must be used to protect the foreign cells (Ostrowski, Wlodarski, Skarzinska and P#{243}ltorak 1970: Wbodarski and Hancox 1972), because their survival after grafting is essential for induction. Rather similarly, by using cortisone as an immunosuppressant it was possible for the first time to reveal that the well known osteoinductive properties of transitional epithelium could be effective across the barrier between species (Wlodarski, P#{243}ltorak, Zaleski and Ostrowski 1971). Though the inducing stimuli in these two experimental systems are apparently quite different-that is, a non-viable product obtained from bone matrix on the one hand, and living cells on the other-the end-results after grafting seem very similar if not identical. In the work described below an attempt has been made to find out more about the comparative properties of the two systems, and in particular to try to answer the following questions. 1) Can induction be obtained when Urist’s material is implanted into an animal ofa different species? The reduction ofthe antigenicity ofbone which has been shown to follow lyophilisation (Kossowska-Paul 1966) seemed an important factor in this question. 2) Is it necessary to use an immunosuppressant for bone induction to be manifest after such implantation? 3) Does immunosuppressant influence cartilage and bone induction when Urist material is used in animals other than rabbits ? 4) Does the actual site of implantation of Urist material influence induction in the same way as do grafts of living epithelial cells? To answer these questions, the decalcified lyophilised rat bone matrix was implanted into various sites in mice with and without cortisone treatment. It was also implanted into gerbils with and without cortisone treatment and into cortisone-treated rabbits. In order to test the immunosuppressive efficacy of the cortisone dosage in the gerbils and rabbits, living xenogenic grafts of the urinary bladder mucosa of the guinea-pig were used as controls. It seems that this is the first report of the use of gerbils in bone induction experiments: for this reason, and because with them we obtained different results from those with other laboratory animals, it was thought worthwhile to gather more information on their response to osteoinductive stimuli. To that end, human amniotic cells of the tissue culture WISH line and allogenic urinary bladder mucosa were grafted i ntramuscularly i nto cortisone-treated gerbils.