Histological Assessment of the Sclerotic Graft-versus-Host Response in the Humanized RAG2(-/-)gamma c(-/-) Mouse Model

Marieke C. H. Hogenes; Suzanne van Dorp; Joyce van Kuik; Filipa R. P. Monteiro; Natalie ter Hoeve; Marijke R. van Dijk; Anton C. Martens; Roel A. de Weger

doi:10.1016/j.bbmt.2012.05.002

Histological Assessment of the Sclerotic Graft-versus-Host Response in the Humanized RAG2(-/-)gamma c(-/-) Mouse Model

Marieke C. H. Hogenes, Suzanne van Dorp, Joyce van Kuik, Filipa R. P. Monteiro, Natalie ter Hoeve, Marijke R. van Dijk, Anton C. Martens, Roel A. de Weger^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Graft-versus-host disease (GVHD) remains a frequently occurring and difficult-to-treat complication in human allogeneic stem cell transplantation. Murine transplantation models are often used to study and understand the complex pathogenesis of GVHD and to explore new treatment strategies. Although GVHD kinetics may differ in murine and human models, adequate models are essential for identification of the crucial factors responsible for the major pathology in GVHD. We present a detailed description of the specific histological features of a graft-versus-host induced fibrotic response in xenogeneic RAG2(-/-)gamma c(-/-) mice after total body irradiation and injection with human peripheral blood mononuclear cells. We describe the full morphological features of this reaction, including a detailed analysis of the specific tissue infiltration patterns of the human peripheral blood mononuclear cells. Our data show the development of fibrosis, predominantly near blood vessels, and reveal different cell populations and specific cell migration patterns in the affected organs. The combination of immunohistochemical cell characterization and mRNA expression analysis of both human (donor)- and murine (host)-derived cytokines reveals an interaction between host tissues and donor-derived cells in an entangled cytokine profile, in which both donor- and host-derived cytokines contribute to the formation of fibrosis. Biol Blood Marrow Transplant 18: 1023-1035 (2012) (C) 2012 American Society for Blood and Marrow Transplantation

Original language	English
Pages (from-to)	1023-1035
Number of pages	13
Journal	Biology of Blood and Marrow Transplantation
Volume	18
Issue number	7
DOIs	https://doi.org/10.1016/j.bbmt.2012.05.002 https://doi.org/10.1016/j.bbmt.2012.05.002
Publication status	Published - Jul 2012

Keywords

Graft-versus-host disease
Mouse model
Histology
Migration patterns
MESENCHYMAL STEM-CELLS
SEVERE COMBINED IMMUNODEFICIENCY
PERIPHERAL-BLOOD LYMPHOCYTES
BONE-MARROW-TRANSPLANTATION
FACTOR GENE-EXPRESSION
HUMAN IMMUNE-SYSTEM
T-CELLS
LOCALIZED SCLERODERMA
INFLAMMATORY CELLS
INTERFERON-GAMMA

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Hogenes, M. C. H., van Dorp, S., van Kuik, J., Monteiro, F. R. P., ter Hoeve, N., van Dijk, M. R., Martens, A. C., & de Weger, R. A. (2012). Histological Assessment of the Sclerotic Graft-versus-Host Response in the Humanized RAG2(-/-)gamma c(-/-) Mouse Model. Biology of Blood and Marrow Transplantation, 18(7), 1023-1035. https://doi.org/10.1016/j.bbmt.2012.05.002, https://doi.org/10.1016/j.bbmt.2012.05.002

@article{7fde5a5ebe564c0f87c52a44eba439f5,

title = "Histological Assessment of the Sclerotic Graft-versus-Host Response in the Humanized RAG2(-/-)gamma c(-/-) Mouse Model",

abstract = "Graft-versus-host disease (GVHD) remains a frequently occurring and difficult-to-treat complication in human allogeneic stem cell transplantation. Murine transplantation models are often used to study and understand the complex pathogenesis of GVHD and to explore new treatment strategies. Although GVHD kinetics may differ in murine and human models, adequate models are essential for identification of the crucial factors responsible for the major pathology in GVHD. We present a detailed description of the specific histological features of a graft-versus-host induced fibrotic response in xenogeneic RAG2(-/-)gamma c(-/-) mice after total body irradiation and injection with human peripheral blood mononuclear cells. We describe the full morphological features of this reaction, including a detailed analysis of the specific tissue infiltration patterns of the human peripheral blood mononuclear cells. Our data show the development of fibrosis, predominantly near blood vessels, and reveal different cell populations and specific cell migration patterns in the affected organs. The combination of immunohistochemical cell characterization and mRNA expression analysis of both human (donor)- and murine (host)-derived cytokines reveals an interaction between host tissues and donor-derived cells in an entangled cytokine profile, in which both donor- and host-derived cytokines contribute to the formation of fibrosis. Biol Blood Marrow Transplant 18: 1023-1035 (2012) (C) 2012 American Society for Blood and Marrow Transplantation",

keywords = "Graft-versus-host disease, Mouse model, Histology, Migration patterns, MESENCHYMAL STEM-CELLS, SEVERE COMBINED IMMUNODEFICIENCY, PERIPHERAL-BLOOD LYMPHOCYTES, BONE-MARROW-TRANSPLANTATION, FACTOR GENE-EXPRESSION, HUMAN IMMUNE-SYSTEM, T-CELLS, LOCALIZED SCLERODERMA, INFLAMMATORY CELLS, INTERFERON-GAMMA",

author = "Hogenes, {Marieke C. H.} and {van Dorp}, Suzanne and {van Kuik}, Joyce and Monteiro, {Filipa R. P.} and {ter Hoeve}, Natalie and {van Dijk}, {Marijke R.} and Martens, {Anton C.} and {de Weger}, {Roel A.}",

year = "2012",

month = jul,

doi = "10.1016/j.bbmt.2012.05.002",

language = "English",

volume = "18",

pages = "1023--1035",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier",

number = "7",

}

Hogenes, MCH, van Dorp, S, van Kuik, J, Monteiro, FRP, ter Hoeve, N, van Dijk, MR, Martens, AC & de Weger, RA 2012, 'Histological Assessment of the Sclerotic Graft-versus-Host Response in the Humanized RAG2(-/-)gamma c(-/-) Mouse Model', Biology of Blood and Marrow Transplantation, vol. 18, no. 7, pp. 1023-1035. https://doi.org/10.1016/j.bbmt.2012.05.002, https://doi.org/10.1016/j.bbmt.2012.05.002

TY - JOUR

T1 - Histological Assessment of the Sclerotic Graft-versus-Host Response in the Humanized RAG2(-/-)gamma c(-/-) Mouse Model

AU - Hogenes, Marieke C. H.

AU - van Dorp, Suzanne

AU - van Kuik, Joyce

AU - Monteiro, Filipa R. P.

AU - ter Hoeve, Natalie

AU - van Dijk, Marijke R.

AU - Martens, Anton C.

AU - de Weger, Roel A.

PY - 2012/7

Y1 - 2012/7

N2 - Graft-versus-host disease (GVHD) remains a frequently occurring and difficult-to-treat complication in human allogeneic stem cell transplantation. Murine transplantation models are often used to study and understand the complex pathogenesis of GVHD and to explore new treatment strategies. Although GVHD kinetics may differ in murine and human models, adequate models are essential for identification of the crucial factors responsible for the major pathology in GVHD. We present a detailed description of the specific histological features of a graft-versus-host induced fibrotic response in xenogeneic RAG2(-/-)gamma c(-/-) mice after total body irradiation and injection with human peripheral blood mononuclear cells. We describe the full morphological features of this reaction, including a detailed analysis of the specific tissue infiltration patterns of the human peripheral blood mononuclear cells. Our data show the development of fibrosis, predominantly near blood vessels, and reveal different cell populations and specific cell migration patterns in the affected organs. The combination of immunohistochemical cell characterization and mRNA expression analysis of both human (donor)- and murine (host)-derived cytokines reveals an interaction between host tissues and donor-derived cells in an entangled cytokine profile, in which both donor- and host-derived cytokines contribute to the formation of fibrosis. Biol Blood Marrow Transplant 18: 1023-1035 (2012) (C) 2012 American Society for Blood and Marrow Transplantation

AB - Graft-versus-host disease (GVHD) remains a frequently occurring and difficult-to-treat complication in human allogeneic stem cell transplantation. Murine transplantation models are often used to study and understand the complex pathogenesis of GVHD and to explore new treatment strategies. Although GVHD kinetics may differ in murine and human models, adequate models are essential for identification of the crucial factors responsible for the major pathology in GVHD. We present a detailed description of the specific histological features of a graft-versus-host induced fibrotic response in xenogeneic RAG2(-/-)gamma c(-/-) mice after total body irradiation and injection with human peripheral blood mononuclear cells. We describe the full morphological features of this reaction, including a detailed analysis of the specific tissue infiltration patterns of the human peripheral blood mononuclear cells. Our data show the development of fibrosis, predominantly near blood vessels, and reveal different cell populations and specific cell migration patterns in the affected organs. The combination of immunohistochemical cell characterization and mRNA expression analysis of both human (donor)- and murine (host)-derived cytokines reveals an interaction between host tissues and donor-derived cells in an entangled cytokine profile, in which both donor- and host-derived cytokines contribute to the formation of fibrosis. Biol Blood Marrow Transplant 18: 1023-1035 (2012) (C) 2012 American Society for Blood and Marrow Transplantation

KW - Graft-versus-host disease

KW - Mouse model

KW - Histology

KW - Migration patterns

KW - MESENCHYMAL STEM-CELLS

KW - SEVERE COMBINED IMMUNODEFICIENCY

KW - PERIPHERAL-BLOOD LYMPHOCYTES

KW - BONE-MARROW-TRANSPLANTATION

KW - FACTOR GENE-EXPRESSION

KW - HUMAN IMMUNE-SYSTEM

KW - T-CELLS

KW - LOCALIZED SCLERODERMA

KW - INFLAMMATORY CELLS

KW - INTERFERON-GAMMA

U2 - 10.1016/j.bbmt.2012.05.002

DO - 10.1016/j.bbmt.2012.05.002

M3 - Article

C2 - 22579931

SN - 1083-8791

VL - 18

SP - 1023

EP - 1035

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 7

ER -

Histological Assessment of the Sclerotic Graft-versus-Host Response in the Humanized RAG2(-/-)gamma c(-/-) Mouse Model

Abstract

Keywords

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