Murine bone marrow derived stromal progenitor cells fail to prevent or treat acute graft-versus-host disease.
Human and murine stromal progenitor cells (SPCs) can suppress alloresponse in vitro, suggesting that SPCs may have clinical application toward prevention or treatment of graft-versus-host disease (GVHD). However, th eresults of in vivo studies have been conflicting. This study utilized an established murine model of acute GVHD to assess the ability of bone marrow derived murine SPCs (mSPCs) to prevent or treat GVHD. GVHD was established by transplantation of B6 bone marrow and spleen cells into lethally irradiated (900 cGy) B6 x BALB/c F(1) recipients. mSPCs were administered using various dose and timing protocols designed to either prevent or treat GVHD. After transplantation, mice were monitored daily for weight and survival. Differences in symptom severity were compared using a clinical GVHD scoring system. All GVHD control mice died of lethal GVHD. All groups treated with mSPCs for the prevention of GVHD went on to develop clinical GVHD with no alteration of the disease course or severity compared to controls. Administration of mSPC after the development of GVHD failed to improve the disease course. We conclude that in this model, the ability of SPCs to suppress alloresponse in vitro does not correlate with in vivo prevention or treatment of acute GVHD.
Badillo
Andrea T
AT
The Children's Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Peranteau
William H
WH
Heaton
Todd E
TE
Quinn
Courtney
C
Flake
Alan W
AW
D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006086:Graft vs Host Disease / Q000517:prevention & control / Q000628:therapy*; D007108:Immune Tolerance; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D017154:Stromal Cells / Q000637:transplantation*; D017211:Treatment Failure