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

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

Author information

1
Division of Oncology, Washington University in St. Louis, St. Louis, Missouri.
2
Division of Dermatology, Washington University in St. Louis, St. Louis, Missouri.

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.

KEYWORDS:

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

PMID:
30204297
PMCID:
PMC6249102
[Available on 2019-12-01]
DOI:
10.1002/cpph.47

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