![]() Consequently, C.B-17-Prkdc scid ( scid) mice, which are defective in rearrangements of T-cell receptor (TCR) and B-cell receptor (BCR) resulting in defects of functional T and B cells, were discovered in 1983. The epoch-making discovery of nude mice by Isaason and Cattanach in 1962 1-mice defective in the thymus with T-cell deficiency-has contributed to progress in this research. It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/γ c null mice.Įfforts to develop animal recipients for xenotransplantation, especially human cells, to establish an animal model for human diseases or to investigate mechanisms during the growth and differentiation of human stem cells have long been pursued. The interferon-γ production from dendritic cells from the NOD/SCID/γ c null mouse spleen was significantly suppressed in comparison with findings in 2 other strains of mice. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/γ c null mice, cytokine production of spleen cells stimulated with Listeria monocytogenesantigens was compared among these 3 strains of mice. These results suggest that NOD/SCID/γ c null mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. Further, even 1 × 10 2 CD34 + cells could grow and differentiate in this strain. In addition to the high engraftment rate, multilineage cell differentiation was also observed. The same high engraftment rate of human mature cells was observed in ascites when peripheral blood mononuclear cells were intraperitoneally transferred. When human CD34 + cells from umbilical cord blood were transplanted into this strain, the engraftment rate in the peripheral circulation, spleen, and bone marrow were significantly higher than that in NOD/Shi- scid mice treated with anti-asialo GM1 antibody or in the β2-microglobulin–deficient NOD/LtSz- scid (NOD/SCID/β2m null) mice, which were as completely defective in NK cell activity as NOD/SCID/γ c null mice. In conclusion, we demonstrated for the first time that allogeneic HSCs from a different inbred strain can compete for niches in the BM compartment of NSG mice.To establish a more appropriate animal recipient for xenotransplantation, NOD/SCID/γ c null mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interleukin-2Rγ (IL-2Rγ) allelic mutation (γ c null) were generated by 8 backcross matings of C57BL/6J-γ c null mice and NOD/Shi- scidmice. Using this novel NSG transplantation model, we will be able to study the effects of low dose in vivo X-ray exposure on the long-term fate of HSCs, without the requirement of prior radio-ablation of the recipient, and thus leaving the recipient’s BM microenvironment uncompromised. Also, in vivo irradiated HSCs showed long-term engraftment, although overall white blood cell (WBC) donor chimerism was lower compared with non-irradiated HSCs. All transplanted NSG mice showed long-term myeloid and lymphoid cell chimerism. ![]() ![]() We transplanted allogeneic HSCs constitutively expressing the mCherry fluorescent marker into age-matched NSG mice and assessed donor chimerism 6 months post-transplantation. Here, we present data on the transplantation of HSCs into NOD scid gamma (NSG) mice to achieve long-term engraftment without prior conditioning. Nevertheless, NOD scid mice have a significantly altered life span due to early development of thymic lymphomas, which compromises the ability to study the long-term fate of exogenous HSCs and their progeny. Scid hematopoietic stem cells (HSCs) have an intrinsic defect in their maintenance within the bone marrow (BM) niche which facilitates HSC transplantation without the absolute requirement of prior conditioning. ![]()
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |