title: Mesenchymal stromal cells engineered to express erythropoietin induce anti-erythropoietin antibodies and anemia in allorecipients.
abstract: Autologous bone marrow mesenchymal stromal cells (MSCs) have been successfully used for the delivery of erythropoietin (EPO) in murine models of anemia and myocardial infarction. For clinical applications where a transient effect would be adequate, such as myocardial infarction, the use of EPO-engineered universal donor allogeneic MSCs would be a substantial convenience. We thus investigated whether MSCs from C57BL/6 mice would permit robust transient EPO delivery in normal BALB/c allorecipients. Implantation of MSCs overexpressing murine EPO led to increases in hematocrit in syngeneic and allogeneic mice, but the latter eventually developed severe anemia due to acquired neutralizing anti-EPO antibodies. As MSCs constitutively produce the CCL2 chemokine which may behave as an adjuvant to the anti-EPO immune response, experiments were performed using EPO-engineered MSCs derived from CCL2(-/-) mice and similar results were obtained. In conclusion, MHC-mismatched MSCs can break the tolerance to autoantigens and lead to the development of pathogenic autoantibodies.
authors.affiliation: The Montreal Center for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Campeau
authors.forename: Moutih
authors.initials: M
authors.lastname: Rafei
authors.forename: Moïra
authors.initials: M
authors.lastname: François
authors.forename: Elena
authors.initials: E
authors.lastname: Birman
authors.forename: Kathy-Ann
authors.initials: KA
authors.lastname: Forner
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
mesh_terms: D000740:Anemia / Q000209:etiology*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017154:Stromal Cells / Q000166:cytology* / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D004921:Erythropoietin