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

PLoS One. 2019 Sep 19;14(9):e0217345. doi: 10.1371/journal.pone.0217345. eCollection 2019.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Disease Models, Animal
  • Fetal Blood / cytology*
  • Graft vs Leukemia Effect / immunology*
  • Hematopoietic Stem Cell Transplantation* / methods
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / therapy
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID

Substances

  • Antigens, CD34

Grants and funding

This work was funded by PG.P. Ministero della Salute (RF 2013-02356924). http://www.salute.gov.it/portale/home.html; Associazione italiana per la ricerca sul cancro (AIRC 2013). https://www.airc.it/; O.T. Associazione italiana per la ricerca sul cancro (AIRC Fellowship 2017, contract number 19499). https://www.airc.it/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.