دورية أكاديمية
Improvement of multilineage hematopoiesis in hematopoietic stem cell-transferred c-kit mutant NOG-EXL humanized mice
| العنوان: | Improvement of multilineage hematopoiesis in hematopoietic stem cell-transferred c-kit mutant NOG-EXL humanized mice |
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| المؤلفون: | Ryoji Ito, Yusuke Ohno, Yunmei Mu, Yuyo Ka, Shuko Ito, Maiko Emi-Sugie, Misa Mochizuki, Kenji Kawai, Motohito Goto, Tomoyuki Ogura, Riichi Takahashi, Akira Niwa, Tatsutoshi Nakahata, Mamoru Ito |
| المصدر: | Stem Cell Research & Therapy, Vol 15, Iss 1, Pp 1-7 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine (General) LCC:Biochemistry |
| مصطلحات موضوعية: | Hematopoietic stem cells, Hematopoiesis, Humanized mice, NOG, CD34+ cells, Medicine (General), R5-920, Biochemistry, QD415-436 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-6512 |
| العلاقة: | https://doaj.org/toc/1757-6512Test |
| DOI: | 10.1186/s13287-024-03799-w |
| الوصول الحر: | https://doaj.org/article/5fb3c7fe2ac54a79a530db9b5302a07cTest |
| رقم الانضمام: | edsdoj.5fb3c7fe2ac54a79a530db9b5302a07c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17576512 |
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| DOI: | 10.1186/s13287-024-03799-w |