[Post-transplant cell immune reconstitution in humanized NOD/SCID mice].

OBJECTIVE

To investigate the cell immune reconstitution in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice by the transplantation of human umbilical cord blood (HUCB) CD34⁺; cells. Methods CD34⁺; cells were isolated from HUCB by magnetic activated cell sorting (MACS), and then were transplanted into NOD/SCID mice following the irradiation of sublethal doses via the lateral tail vein. Human CD45⁺; CD3⁺; CD56⁺; cell populations in the peripheral blood of mice were dynamically analyzed by flow cytometry (FCM) 4, 6, 8 and 10 weeks after transplantation. After 10 weeks, the expression of human ALU gene was detected by PCR in the bone marrow of mice, and the expressions of human CD3⁺; CD56⁺; cells were examined by immunohistochemical staining in the spleen tissues.

RESULTS

After irradiation, the nucleated cells and giant cells in the marrow cavity of NOD/SCID mice were reduced significantly or completely demolished. The effect of myeloablative pretreatment was ideal. Human CD45⁺; CD3⁺; CD56⁺; cells were found by FCM in the peripheral blood of all surviving mice in transplantation group 4, 6, 8, and 10 weeks after the transplantation. The population of the human lymphocytes varied over time, peaked at the 8th week, and remained at a high level later. At the 10th week, the human ALU sequence could be detected in the bone marrow of all surviving mice in transplantation group, and human CD3⁺; CD56⁺; cells could be observed in the spleen tissues. All mice which received no transplantation died within 2 weeks after irradiation.

CONCLUSION

The hu-SRC-NOD/SCID model was successfully established in irradiation-induced NOD/SCID mice by the transplantation of HUCB CD34⁺; cells, and its cell immune system was effectively rebuilt.