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Human cord blood (hCB)-CD34+ humanized mice fail to reject human acute myeloid leukemia cells


Autoři: Olga Tanaskovic aff001;  Maria Vittoria Verga Falzacappa aff001;  Pier Giuseppe Pelicci aff001
Působiště autorů: Department of Experimental Oncology at the IEO, European Institute of Oncology IRCCS, Milan, Italy aff001;  Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0217345

Souhrn

Since their appearance, humanized mice carrying human immune system seemed promising tools to study the crosstalk between cancer and immunity. The NOD-scidIL2Rgammanull (NSG) mice engrafted with human cord blood (hCB)-CD34+ cells have been proposed to be a valuable tool to reproduce human immune system in mouse. However, the lack of solid evidences on the functionality of their human immune components limits their usage in immune-oncology. We report that (hCB)-CD34+ cells lose their ability to propagate and originate bone marrow-derived human immune cells after two serial transplantations in NSG mice. We demonstrate that transplants of bone marrow patient-derived acute myeloid leukemias (hAMLs) grow very similarly in the humanized (hCB)-CD34+ NSG and parental NSG mice. The similar extent of engraftment and development of leukemias in (hCB)-CD34+ NSG and controls suggests a poor human immune response against not compatible hAMLs. Our findings suggest that (hCB)-CD34+ NSG mice are transient and/or incomplete carriers of the human immune system and, therefore, represent a suboptimal tool to study the interaction between tumor and immune cells.

Klíčová slova:

Research and analysis methods – Animal studies – Experimental organism systems – Model organisms – Mouse models – Animal models – Biology and life sciences – Cell biology – Cellular types – Animal cells – Blood cells – White blood cells – T cells – Immune cells – Physiology – Spleen – Anatomy – Body fluids – Blood – Medicine and health sciences – Immunology – Immune system – Oncology – Cancers and neoplasms – Hematologic cancers and related disorders – Leukemias – Hematology – Surgical and invasive medical procedures – Blood and lymphatic system procedures – Bone marrow transplantation – Stem cell transplantation – Transplantation – Cell transplantation – Immune physiology


Zdroje

1. Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research. Nat Rev Immunol. 2007;7: 118. doi: 10.1038/nri2017 17259968

2. Walsh NC, Kenney LL, Jangalwe S, Aryee K-E, Greiner DL, Brehm MA, et al. Humanized Mouse Models of Clinical Disease. Annu Rev Pathol Mech Dis. 2017;12: 187–215. doi: 10.1146/annurev-pathol-052016-100332 27959627

3. Wiekmeijer A-S, Pike-Overzet K, Brugman MH, Salvatori DCF, Egeler RM, Bredius RGM, et al. Sustained Engraftment of Cryopreserved Human Bone Marrow CD34 + Cells in Young Adult NSG Mice. BioResearch Open Access. 2014;3: 110–116. doi: 10.1089/biores.2014.0008 24940562

4. Cytokine Stimulation of Multilineage Hematopoiesis from Immature Human Cells Engrafted in SCID Mice Author(s): Tsvee Lapidot, Francoise Pflumio, Monica Doedens, Barbara Murdoch, Douglas E. Williams and John E. Dick. Sci New Ser. 1992;255: 1137–1141.

5. Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol. 1995;154: 180. 7995938

6. Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, et al. Human Lymphoid and Myeloid Cell Development in NOD/LtSz-scid IL2Rγnull Mice Engrafted with Mobilized Human Hemopoietic Stem Cells. J Immunol. 2005;174: 6477. doi: 10.4049/jimmunol.174.10.6477 15879151

7. Ito M. NOD/SCID/gamma cnull mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100: 3175–3182. doi: 10.1182/blood-2001-12-0207 12384415

8. Ishikawa F. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor chainnull mice. Blood. 2005;106: 1565–1573. doi: 10.1182/blood-2005-02-0516 15920010

9. King MA, Covassin L, Brehm MA, Racki W, Pearson T, Leif J, et al. Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft- versus -host-like disease and the role of host major histocompatibility complex. Clin Exp Immunol. 2009;157: 104–118. doi: 10.1111/j.1365-2249.2009.03933.x 19659776

10. Greenblatt MB, Vbranac V, Tivey T, Tsang K, Tager AM, Aliprantis AO. Graft versus Host Disease in the Bone Marrow, Liver and Thymus Humanized Mouse Model. Stoddart CA, editor. PLoS ONE. 2012;7: e44664. doi: 10.1371/journal.pone.0044664 22957096

11. Watanabe Y, Takahashi T, Okajima A, Shiokawa M, Ishii N, Katano I, et al. The analysis of the functions of human B and T cells in humanized NOD/shi-scid/γcnull (NOG) mice (hu-HSC NOG mice). Int Immunol. 2009;21: 843–858. doi: 10.1093/intimm/dxp050 19515798

12. Morton JJ, Bird G, Refaeli Y, Jimeno A. Humanized Mouse Xenograft Models: Narrowing the Tumor–Microenvironment Gap. Cancer Res. 2016;76: 6153–6158. doi: 10.1158/0008-5472.CAN-16-1260 27587540

13. Liu D, Song L, Wei J, Courtney AN, Gao X, Marinova E, et al. IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity. J Clin Invest. 2012;122: 2221–2233. doi: 10.1172/JCI59535 22565311

14. Aspord C, Leccia M-T, Charles J, Plumas J. Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL. Cancer Immunol Res. 2013;1: 402–415. doi: 10.1158/2326-6066.CIR-13-0114-T 24778133

15. Verga Falzacappa MV, Ronchini C, Reavie LB, Pelicci PG. Regulation of self-renewal in normal and cancer stem cells: Role of stem cell self-renewal in cancer. FEBS J. 2012;279: 3559–3572. doi: 10.1111/j.1742-4658.2012.08727.x 22846222


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