title: Approaches to avoid immune responses induced by repeated subcutaneous injections of allogeneic umbilical cord tissue-derived cells.
abstract: BACKGROUND
  Cellular treatments for repairing diseased tissues represent a promising clinical strategy. Umbilical cord tissue-derived cells (UTC) are a unique source of cells with a low immunogenic profile and potential for tissue repair. By using UTC from miniature swine, we previously demonstrated that despite their low immunogenic phenotype, UTC could induce an immune response under certain inflammatory conditions and after multiple subcutaneous (SC) injections. Given that repeat dosing of cells may be necessary to achieve a lasting therapeutic benefit, in this study, we examined approaches to avoid an immune response to multiple SC injections of UTC.
  
  
  METHODS
  By using in vitro and in vivo measures of sensitization to SC cellular injections, we assessed the effects of varying the location of administration site, prolongation of timing between injections, and use of immunosuppressive treatments on repeated cellular injections in Massachusetts General Hospital major histocompatibility complex-defined miniature swine.
  
  
  RESULTS
  Although under normal conditions, a single SC injection of major histocompatibility complex-mismatched UTC did not induce a detectable immune response, multiple SC injections of UTC demonstrated rapid humoral and cell-mediated immune responses. Avoidance of an immune response to repeat SC injection was achieved by concurrent immunosuppression with each dose of UTC.
  
  
  CONCLUSIONS
  UTC and other similar cell types believed to be nonimmunogenic have the potential to induce immune responses under certain conditions. These studies provide important considerations and guidelines for preclinical studies investigating allogeneic cellular therapies.
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors: Bram V
authors: BV
authors: Lutton
authors: Patricia S
authors: PS
authors: Cho
authors: Erica L
authors: EL
authors: Hirsh
authors: Kelly K
authors: KK
authors: Ferguson
authors: Alexander G S
authors: AG
authors: Teague
authors: John S
authors: JS
authors: Hanekamp
authors: Nina
authors: N
authors: Chi
authors: Stephanie N
authors: SN
authors: Goldman
authors: Darin J
authors: DJ
authors: Messina
authors: Stuart
authors: S
authors: Houser
authors: Beow Y
authors: BY
authors: Yeap
authors: Sicco H
authors: SH
authors: Popma
authors: David H
authors: DH
authors: Sachs
authors: Christene A
authors: CA
authors: Huang
mesh_terms: D000818:Animals; D017690:Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D016572:Cyclosporine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007518:Isoantibodies / Q000096:biosynthesis; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014181:Transplantation Immunology; D014470:Umbilical Cord / Q000166:cytology* / Q000276:immunology*
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016572:Cyclosporine; D011239:Prednisolone