Academic Journal
CD47;Rag2;IL-2rγ triple knock-out mice pre-conditioning with busulfan could be a novel platform for generating hematopoietic stem cells engrafted humanized mice
| العنوان: | CD47;Rag2;IL-2rγ triple knock-out mice pre-conditioning with busulfan could be a novel platform for generating hematopoietic stem cells engrafted humanized mice |
|---|---|
| المؤلفون: | Kim, Kang-Hyun, Lee, Sang-wook, Baek, In-Jeoung, Song, Hye-Young, Jo, Seon-Ju, Ryu, Je-Won, Ryu, Seung-Hee, Seo, Jin-Hee, Kim, Jong-Choon, Heo, Seung-Ho |
| المصدر: | Frontiers in Immunology ; volume 15 ; ISSN 1664-3224 |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2024 |
| المجموعة: | Frontiers (Publisher - via CrossRef) |
| الوصف: | Introduction Humanized mouse models to recapitulate human biological systems still have limitations, such as the onset of lethal graft-versus-host disease (GvHD), a variable success rate, and the low accessibility of total body irradiation (TBI). Recently, mice modified with the CD47-SIRPA axis have been studied to improve humanized mouse models. However, such trials have been rarely applied in NOD mice. In this study, we created a novel mouse strain, NOD-CD47 null Rag2 null IL-2rγ null (RTKO) mice, and applied it to generate humanized mice. Methods Four-week-old female NOD-Rag2 null IL-2rγ null (RID) and RTKO mice pre-conditioned with TBI or busulfan (BSF) injection were used for generating human CD34+ hematopoietic stem cell (HSC) engrafted humanized mice. Clinical signs were observed twice a week, and body weight was measured once a week. Flow cytometry for human leukocyte antigens was performed at intervals of four weeks or two weeks, and mice were sacrificed at 48 weeks after HSC injection. Results For a long period from 16 to 40 weeks post transplantation, the percentage of hCD45 was mostly maintained above 25% in all groups, and it was sustained the longest and highest in the RTKO BSF group. Reconstruction of human leukocytes, including hCD3, was also most prominent in the RTKO BSF group. Only two mice died before 40 weeks post transplantation in all groups, and there were no life-threatening GvHD lesions except in the dead mice. The occurrence of GvHD has been identified as mainly due to human T cells infiltrating tissues and their related cytokines. Discussion Humanized mouse models under all conditions applied in this study are considered suitable models for long-term experiments based on the improvement of human leukocytes reconstruction and the stable animal health. Especially, RTKO mice pretreated with BSF are expected to be a valuable platform not only for generating humanized mice but also for various immune research fields. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| DOI: | 10.3389/fimmu.2024.1365946 |
| DOI: | 10.3389/fimmu.2024.1365946/full |
| الاتاحة: | http://dx.doi.org/10.3389/fimmu.2024.1365946 https://www.frontiersin.org/articles/10.3389/fimmu.2024.1365946/full |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.EB2A88CF |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2024.1365946 |
|---|