Establishment Of Mouse Model Engrafted By Human Cord Blood Hematopoietic Stem Cells

As a main method to treat blood and immune diseases,Hematopoietic stem cell transplantation can also be used to establish mouse model for many kinds of diseases, especially the humanized-blood mouse model for virus which can not infect mouse naturally.In this article,CD34 positive cells were isolated from human cord blood and transplanted into mouse by bone marrow transplantation(BMT),neonatal liver transplantation(NLT) and In utero transplantation(IUT),respectively.1 month to 3 months after transplantation,hCD45 were inspected for human blood cells in bone marrow and periphercal blood.In NLT group,myeloid and lymphoid lineages markers,hCD33,hCD3 and hCD19 were also inspected in bone marrow,peripheral blood and spleen,human cells engraftment were detected in mouse by FACS analyses for these markers.1.12 NOD/SCID mice were transplantated by BMT,including 4 mice in negative control group and 8 mice transplanted by human cells.Engraftment was observed in all those mice with the highest level of 46%human-CD45 positive cells in peripheral blood after 1 month and 96%in bone marrow after 3 months.This suggested the human cells engraftment in NOD/SCID mice could be greatly promoted by BMT.2.16 neonatal NOD/SCID mice were transplanted by NLT,including 4 mice as negative control and 12 mice transplanted with human cells.Negative mice died within 2 weeks with no engraftment.3 mice transplanted with human cells survived 2 months.Engraftment was observed with 26%human-CD45 positive cells after 1 month and 60%in peripheral blood,86%in bone marrow after 2 months.T,B, myeloid cells were detected in spleen,bone marrow and peripheral blood after 2 months,the percentages were 4.29%,47.27%and 5.40%in spleen,0.25%,54.27% and 23.50%in bone marrow,0.70%,26.42%and 2.69%in peripheral blood, respectively.This suggested NLT is an effective method to establish human blood cells engraftment in NOD/SCID mice with both myeloid and lymphoid lineages.3.22 ICR mice were born after transplanted by E8.5d IUT,human CD45 positive cells were detected in 17 mice,the level in 16 mice was below 1%with only one mice reach 4.34%.8 ICR mice were born after transplanted by E12.5d IUT with 6 mice engrafted with human CD45 positive cells,the level was lower than that of E8.5 IUT group.11 NOD/SCID mice were born after E8.5d IUT and engraftment were also observed below 1%.This results suggested E8.5d IUT is superior than E12.5d IUT,however,the engraftment of IUT is quite lower than other methods. Additionally,NOD/SCID mice were not superior to ICR mice by E8.5 IUT method to get higher engraftment.