CD34+ humanized mice are model animals constructed by transportation of human umbilical cord blood and fetal liver hematopoietic stem cells (HSCs) into irradiated myeloablative M-NSG mice. HSCs can colonize in the bone marrow of mice after transplantation and continuously produce various types of hematopoietic or immune cells, such as T cells, B cells, NK cells, and myeloid cells. Since the immune cells are developed in mice and are tolerant to the host, no GvHD will be observed, human-derived immune cells will exist stably, and the types of reconstructed immune cells will be richer than those of PBMC humanized mice. However, the T cell function of this model type is relatively weak due to lack of human thymus required for human T cell development. In addition, the myeloid cells of this model are underdeveloped, and the content of NK cells is relatively low, because the species differences between humans and mice are demonstrated by certain cytokines that regulate the development of these two types of cells.
IL-15 is essential for the development of NK cells, natural killer T cells, and memory CD8+ T cells. The supplementation of human IL-15 by Shanghai Model Organisms Center on the basis of conventional CD34+ humanized mice is able to significantly increase the proportion of NK cells to be suitable for the efficacy evaluation of drug targets on NK cells.
Figure 1. Preparation process of M-NSG mice transplanted with human hematopoietic stem cells (HSCs).
Figure 2. Reconstructed hematopoietic system of M-NSG mice transplanted with human hematopoietic stem cells (HSCs), indicating continuously increased level of human-derived CD45+ immune cells in peripheral blood.
Figure 3. Proportions of various types of hematopoietic/immune cells at 20 weeks after the mice are transplanted with human hematopoietic stem cells (HSCs), including human-derived T (CD3+CD4+ and CD3+CD8+ cells), B (CD19+ cells), NK lymphocytes (CD56+CD16+ cells), and monocytes (CD14+CD11b+ cells).
Figure 4. Reconstructed hematopoietic system of M-NSG mice transplanted with human hematopoietic stem cells (HSCs), with supplementation of human-derived IL-15, which can significantly increase the proportion of NK cells and is suitable for the efficacy evaluation of drug targets on NK cells.
Figure 5. Example 1 of anti-tumor efficacy validation in Hu-HSC tumor-bearing mouse model
Figure 6. Example 2 of anti-tumor efficacy validation in Hu-HSC tumor-bearing mouse model
Hematological disease study
Infectious disease study
Study on drug targets without cross reactions
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SMOC’s Annual Progress and Advances in Preclinical immuno-Oncology Research: The workshop is designed as a forum for ideas and opinions exchange on how to decrease the rate of clinical failures in oncology and immuno-oncology.조회
After the base is put into operation, SMOC’s capability to provide genetically modified rat/mouse models and technical services including gene function research and drug development will be greatly enhanced.조회