title: Delivery of erythropoietin by encapsulated myoblasts in a genetic model of severe anemia.
abstract: BACKGROUND
  Existing animal models of anemia inadequately reflect the hematocrit usually present in chronic renal failure (CRF) patients and do not permit long-term treatment studies. The transgenic mouse strain 134.3LC (Epo-TAg(H)) displays a severe chronic anemia resembling that observed clinically during CRF, while displaying an active, normal life span. This phenotype makes it a particularly interesting mouse model for testing erythropoietin (Epo)-based gene transfer strategies.
  
  
  METHODS
  Ex vivo gene therapy was employed to administer mouse Epo to homozygous anemic Epo-TAg(H) mice. Encapsulated C(2)C(12) myoblasts genetically engineered to secrete 163 IU mouse Epo/10(6) cells/day were subcutaneously transplanted on the dorsal flank of the mice. Efficacy of delivered Epo was monitored by weekly measurements of animal hematocrit.
  
  
  RESULTS
  Most treated homozygous Epo-TAg(H) mice displayed only a transient rise in hematocrit before eventually decreasing to levels as low as 3%. Administering the immunosuppressor anti-CD4+ monoclonal antibody (mAb) to homozygous Epo-TAg(H) mice, beginning at the time of implantation, permitted a rise in hematocrit that remained stable at elevated levels in cases of continued immunosuppression.
  
  
  CONCLUSIONS
  Mice having the T antigen insertion in both Epo alleles appeared to develop an immune response to the natural mouse Epo delivered by encapsulated cells. By preventing this reaction using immunosuppression, we demonstrate that encapsulated myoblasts can deliver therapeutic doses of mouse Epo systemically and restore hemopoiesis in a genetic model of severe anemia.
authors.affiliation: Modex Thérapeutiques, Lausanne, Switzerland.
authors.forename: Christopher
authors.initials: C
authors.lastname: Rinsch
authors.forename: Phillipe
authors.initials: P
authors.lastname: Dupraz
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Schneider
authors.forename: Nicole
authors.initials: N
authors.lastname: Déglon
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ratcliffe
authors.forename: Patrick
authors.initials: P
authors.lastname: Aebischer
mesh_terms: D000740:Anemia / Q000209:etiology / Q000235:genetics* / Q000628:therapy*; D000818:Animals; D002214:Capsules; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000235:genetics*; D015316:Genetic Therapy; D006400:Hematocrit; D006720:Homozygote; D007165:Immunosuppression Therapy; D007676:Kidney Failure, Chronic / Q000150:complications; D051379:Mice; D008822:Mice, Transgenic; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D019737:Transplants; D016896:Treatment Outcome
chemical_list: D002214:Capsules; D004921:Erythropoietin