A Humanized Ossicle-niche Xenotransplantation Model Enables Improved Human Leukemic Engraftment

This study introduces a new xenotransplantation model where human bone marrow mesenchymal stromal cells are used to create a humanized bone marrow microenvironment (ossicles) in mice. These ossicles support the engraftment of normal and malignant human hematopoietic cells. The humanized ossicles showed superior engraftment of normal human hematopoietic stem and progenitor cells compared to unmanipulated mice. They also demonstrated enhanced engraftment of diverse primary acute myeloid leukemia samples. Direct transplantation into the ossicles accelerated engraftment and increased leukemia-initiating cell frequencies. This model facilitates the study of human hematologic diseases and their interactions within a humanized microenvironment.

• 1
  Humanized ossicles exhibit robust engraftment of normal human hematopoietic stem and progenitor cells.
• 2
  Primary acute leukemia cells, including AML, B-ALL, and T-ALL, engraft at high levels in the humanized ossicles, often leading to complete replacement of the mouse bone marrow.
• 3
  The humanized ossicle model supports the engraftment of acute promyelocytic leukemia (APL) cells, which have been difficult to engraft in traditional xenotransplantation models, and identifies leukemia-initiating cells in a committed myeloid progenitor population.