title: A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells.
abstract: Xenotransplantation models represent powerful tools for the investigation of healthy and malignant human hematopoiesis. However, current models do not fully mimic the components of the human bone marrow (BM) microenvironment, and they enable only limited engraftment of samples from some human malignancies. Here we show that a xenotransplantation model bearing subcutaneous humanized ossicles with an accessible BM microenvironment, formed by in situ differentiation of human BM-derived mesenchymal stromal cells, enables the robust engraftment of healthy human hematopoietic stem and progenitor cells, as well as primary acute myeloid leukemia (AML) samples, at levels much greater than those in unmanipulated mice. Direct intraossicle transplantation accelerated engraftment and resulted in the detection of substantially higher leukemia-initiating cell (LIC) frequencies. We also observed robust engraftment of acute promyelocytic leukemia (APL) and myelofibrosis (MF) samples, and identified LICs in these malignancies. This humanized ossicle xenotransplantation approach provides a system for modeling a wide variety of human hematological diseases.
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.|Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reinisch
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.|Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.|Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: M Ryan
authors.initials: MR
authors.lastname: Corces
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.|Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Dita
authors.identifier: 0000-0002-9182-8123
authors.initials: D
authors.lastname: Gratzinger
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.|Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Wan-Jen
authors.initials: WJ
authors.lastname: Hong
authors.affiliation: Department of Blood Group Serology and Transfusion Medicine, Paracelsus Medical University, Salzburg, Austria.|Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schallmoser
authors.affiliation: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria.|Experimental and Clinical Cell Therapy Institute, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Dirk
authors.initials: D
authors.lastname: Strunk
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.|Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Majeti
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D016025:Bone Transplantation; D001842:Bone and Bones; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005312:Fetal Blood; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D015473:Leukemia, Promyelocytic, Acute; D059630:Mesenchymal Stem Cells; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D055728:Primary Myelofibrosis; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment