Human osteoblasts survive and deposit new bone when human bone is implanted in SCID mouse.

Abstract

We describe the first successful engraftment of viable human bone that maintains human osteoblast function and deposits new bone after implantation into pretreated SCID (Hu-bone-SCID) mice. The pretreatment consists of radiation before bone implantation and subsequent administration of antiasialo GM1 antisera every 7 days to deplete mouse macrophage and natural killer (NK) cell activity. The implanted bone samples were analyzed at various times up to 8 weeks. Comparison of pre- and post-implanted human specimens in untreated and pretreated SCID mice showed that while specimens underwent resorption and necrosis in untreated SCID mice, the structure of the implanted bone was preserved in the pretreated Hu-bone-SCID mice. In addition, histochemistry and histomorphometric analysis combined with tetracycline labeling showed that new bone formed in in the implants in the pretreated SCID mice. That the new bone resulted from the activity of the implanted human bone cells rather than from induction of differentiation of host mesenchymal cells into mouse osteoblasts was shown by immunohistochemical analysis with two different monoclonal 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 implanted from young (4-9 years) vs. adult (67-82 years) individuals. This model will be useful to investigate and compare endogenous osteoblast activity in different bone samples without the variables of isolating cells and examining them in vitro.