Bibliographic Details
| Title: |
Improvement of multilineage hematopoiesis in hematopoietic stem cell-transferred c-kit mutant NOG-EXL humanized mice. |
| Authors: |
Ito, Ryoji1 (AUTHOR) rito@ciea.or.jp, Ohno, Yusuke1 (AUTHOR), Mu, Yunmei1,2 (AUTHOR), Ka, Yuyo1 (AUTHOR), Ito, Shuko1 (AUTHOR), Emi-Sugie, Maiko1 (AUTHOR), Mochizuki, Misa1 (AUTHOR), Kawai, Kenji1 (AUTHOR), Goto, Motohito1 (AUTHOR), Ogura, Tomoyuki1 (AUTHOR), Takahashi, Riichi1 (AUTHOR), Niwa, Akira3 (AUTHOR), Nakahata, Tatsutoshi1 (AUTHOR), Ito, Mamoru1 (AUTHOR) |
| Source: |
Stem Cell Research & Therapy. 6/21/2024, Vol. 15 Issue 1, p1-7. 7p. |
| Subject Terms: |
*HEMATOPOIESIS, *C-kit protein, *GRANULOCYTE-macrophage colony-stimulating factor, *HEMATOPOIETIC stem cells, *HUMAN stem cells, *PROTEIN-tyrosine kinases |
| Abstract: |
Human hematopoietic stem cell (HSC)-transferred humanized mice are valuable models for exploring human hematology and immunology. However, sufficient recapitulation of human hematopoiesis in mice requires large quantities of enriched human CD34+ HSCs and total-body irradiation for adequate engraftment. Recently, we generated a NOG mouse strain with a point mutation in the c-kit tyrosine kinase domain (W41 mutant; NOGW mice). In this study, we examined the ability of NOGW mice to reconstitute human hematopoietic cells. Irradiated NOGW mice exhibited high engraftment levels of human CD45+ cells in the peripheral blood, even when only 5,000–10,000 CD34+ HSCs were transferred. Efficient engraftment of human CD45+ cells was also observed in non-irradiated NOGW mice transferred with 20,000–40,000 HSCs. The bone marrow (BM) of NOGW mice exhibited significantly more engrafted human HSCs or progenitor cells (CD34+CD38− or CD34+CD38+ cells) than the BM of NOG mice. Furthermore, we generated a human cytokine (interleukin-3 and granulocyte-macrophage colony-stimulating factor) transgenic NOG-W41 (NOGW-EXL) mouse to achieve multilineage reconstitution with sufficient engraftment of human hematopoietic cells. Non-irradiated NOGW-EXL mice showed significantly higher engraftment levels of human CD45+ and myeloid lineage cells, particularly granulocytes and platelets/megakaryocytes, than non-irradiated NOGW or irradiated NOG-EXL mice after human CD34+ cell transplantation. Serial BM transplantation experiments revealed that NOGW mice exhibited the highest potential for long-term HSC compared with other strains. Consequently, c-kit mutant NOGW-EXL humanized mice represent an advanced model for HSC-transferred humanized mice and hold promise for widespread applications owing to their high versatility. Significance statement: Humanized mice engrafted with human hematopoietic stem cells (HSCs) can reconstitute the human hematologic environment and are valuable in hematology and immunology research. Standard methods require large numbers of enriched CD34+ HSCs and whole-body irradiation to achieve sufficient engraftment in humanized mice. Here, we examined human hematopoietic cell reconstitution in a NOG mouse strain with a point mutation in the c-kit tyrosine kinase domain (NOGW and NOGW-EXL mice). Our findings revealed that NOGW and NOGW-EXL mice present an irradiation-free approach for the efficient engraftment of multilineage human hematopoietic cells and require a reduced number of CD34+ HSCs for transplantation. [ABSTRACT FROM AUTHOR] |
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