HUMAN OSTEOBLASTS SURVIVE AND DEPOSIT NEW BONE WHEN HUMAN BONE IS IMPLANTED IN SCID MOUSE

We describe the first successful engraftment of viable human bone that maintains human osteoblast function and deposits new bone after impla ntation into pretreated SCID (Hu-bone-SCID) mice, The pretreatment con sists of radiation before bone implantation and subsequent administrat ion of antiasialo GM1 antisera every 7 days to deplete mouse macrophag e and natural killer (NK) cell activity. The implanted bone samples we re analyzed at various times up to 8 weeks, Comparison of pre- and pos timplanted human specimens in untreated and pretreated SCID mice showe d that while specimens underwent resorption and necrosis in untreated SCID mice, the structure of the implanted bone was preserved in the pr etreated Hu-bone-SCID mice, In addition, histochemistry and histomorph ometric analysis combined with tetracycline labeling showed that new b one formed in the implants in the pretreated SCID mice, That the new b one resulted from the activity of the implanted human bone cells rathe r than from induction of differentiation of host mesenchymal cells int o mouse osteoblasts was shown by immunohistochemical analysis with two different moneclonal antibodies (mAb), one mAb recognizing human HLA class II antigens and one recognizing human osteoblasts and osteocytes , Donor variability was observed in the implanted bone; however, bone from the same donor maintained its characteristics in all Hu-bone-SCID mice, and striking quantitative differences were seen in bone implant ed from young (4-9 years) vs, adult (67-82 years) individuals, This mo del will be useful to investigate and compare endogenous osteoblast ac tivity in different bone samples without the variables of isolating ce lls and examining them in vitro.