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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


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