Modeling Chronic Graft Versus Host Disease in Mice Using Allogeneic Bone Marrow and Splenocyte Transfer

Curr Protoc Pharmacol. 2018 Dec;83(1):e47. doi: 10.1002/cpph.47. Epub 2018 Sep 11.

Abstract

This unit describes a method for allogeneic bone marrow and splenocyte transfer for the modeling of chronic graft versus host disease (cGVHD) in mice. Preclinical models provide clinically relevant platforms for mechanistic and therapeutic studies that may inform the treatment of patients suffering from cGVHD, a common and potentially severe complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Most murine models of cGVHD depend on the transfer of major histocompatibility complex (MHC)-mismatched bone marrow and whole splenocytes (or purified T cells) into an irradiated recipient. The bone marrow contains hematopoietic stem and progenitor cells necessary to reconstitute the irradiated host hematopoietic system, while splenocytes contain T cells that mediate cGVHD. Of note, specific mouse strains, splenocyte dose, bone marrow quantity, and irradiation doses vary widely across different cGVHD models. Here we describe donor bone marrow and splenocyte preparation, recipient irradiation and intravenous injection of donor cells, and clinical monitoring for disease emergence and progression. © 2018 by John Wiley & Sons, Inc.

Keywords: allogeneic hematopoietic stem cell transplantation; disease modeling; graft versus host disease; splenocyte transfer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / immunology
  • Bone Marrow / pathology*
  • Bone Marrow Transplantation / adverse effects*
  • Cells, Cultured
  • Chronic Disease
  • Disease Models, Animal
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology*
  • Major Histocompatibility Complex
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Spleen / cytology*
  • Spleen / immunology
  • Spleen / pathology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • T-Lymphocytes / transplantation*
  • Transplantation, Homologous