In vivo expansion of co-transplanted T cells impacts on tumor re-initiating activity of human acute myeloid leukemia in NSG mice

Malte von Bonin; Martin Wermke; Kadriye Nehir Cosgun; Christian Thiede; Martin Bornhauser; Gerard Wagemaker; Claudia Waskow

doi:10.1371/journal.pone.0060680

In vivo expansion of co-transplanted T cells impacts on tumor re-initiating activity of human acute myeloid leukemia in NSG mice

PLoS One. 2013 Apr 9;8(4):e60680. doi: 10.1371/journal.pone.0060680. Print 2013.

Authors

Malte von Bonin¹, Martin Wermke, Kadriye Nehir Cosgun, Christian Thiede, Martin Bornhauser, Gerard Wagemaker, Claudia Waskow

Affiliation

¹ Regeneration in Hematopoiesis, Center for Regenerative Therapies Dresden - CRTD, DFG Research Center and Cluster of Excellence, Technische Universität Dresden, Dresden, Germany.

Abstract

Human cells from acute myeloid leukemia (AML) patients are frequently transplanted into immune-compromised mouse strains to provide an in vivo environment for studies on the biology of the disease. Since frequencies of leukemia re-initiating cells are low and a unique cell surface phenotype that includes all tumor re-initiating activity remains unknown, the underlying mechanisms leading to limitations in the xenotransplantation assay need to be understood and overcome to obtain robust engraftment of AML-containing samples. We report here that in the NSG xenotransplantation assay, the large majority of mononucleated cells from patients with AML fail to establish a reproducible myeloid engraftment despite high donor chimerism. Instead, donor-derived cells mainly consist of polyclonal disease-unrelated expanded co-transplanted human T lymphocytes that induce xenogeneic graft versus host disease and mask the engraftment of human AML in mice. Engraftment of mainly myeloid cell types can be enforced by the prevention of T cell expansion through the depletion of lymphocytes from the graft prior transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Animals
Bone Marrow Transplantation / immunology
Bone Marrow Transplantation / mortality
Bone Marrow Transplantation / pathology*
Cell Proliferation
Female
Graft vs Host Disease / immunology
Graft vs Host Disease / pathology*
Humans
Leukemia, Myeloid, Acute / immunology
Leukemia, Myeloid, Acute / pathology*
Lymphocyte Depletion
Male
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Myeloid Cells / immunology
Myeloid Cells / pathology*
Neoplasm Transplantation
Survival Analysis
T-Lymphocytes / immunology
T-Lymphocytes / pathology*
Transplantation Chimera
Transplantation, Heterologous / immunology
Transplantation, Heterologous / mortality
Transplantation, Heterologous / pathology*
Whole-Body Irradiation

Grants and funding

CW is supported by the CRTD - DFG Research Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden. This work was supported by a grant of the Deutsche Forschungsgemeinschaft (DFG) Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD) and SFB 655 (#B9, Waskow, Gerok rotation position, #B2, Bornhäuser). The project was further supported by an intramural CRTD-seed grant and a grant from the European Union FP7 CELL-PID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.