Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model

Tissue Eng Part A. 2009 Sep;15(9):2677-86. doi: 10.1089/ten.TEA.2008.0566.

Abstract

Adipose-derived stem cells (ASCs) express a nonimmunogenic profile as shown by in vitro studies that demonstrate a lack of T cell proliferation to allogeneic ASCs as well as ASC-mediated suppression of mixed lymphocyte reactions. To determine whether these observations would translate in vivo, immune monitoring studies were carried out in conjunction with a rat spinal fusion study. ASCs derived from Fischer or ACI strain rats were loaded onto scaffolds and implanted in Fischer recipients that had undergone the following treatments: (1) No treatment; (2) Scaffold only; (3) Syngeneic ASCs+Scaffold; or (4) Allogeneic ASCs+Scaffold. Half of each group was sacrificed at 4 weeks postimplantation, and the remaining animals were sacrificed at 8 weeks. As determined in a separate study, allogeneic and syngeneic ASCs were equally efficacious in accelerating spinal fusion compared to No treatment and Scaffold only control groups. To determine whether donor ASCs induced an immune response in recipient rats, lymph nodes were harvested for T cell proliferation studies and serum was collected to assess antibody responses. Although T cell priming was not detected to donor alloantigens in recipients at either time point, significant antibody responses were detected to ACI ASCs in animals implanted with syngeneic or allogeneic ASCs. Antibodies were of the IgG isotype, noncytotoxic in the presence of complement, and reactive to fetal bovine serum. These results support the use of allogeneic ASCs for spinal fusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Antibodies / metabolism
  • Antibody Formation / drug effects
  • Antibody Formation / immunology
  • Cell Proliferation / drug effects
  • Concanavalin A / pharmacology
  • Flow Cytometry
  • Immune Tolerance
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Models, Animal
  • Phenotype
  • Rats
  • Rats, Inbred F344
  • Spinal Fusion*
  • Spleen / cytology
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Transplantation, Homologous

Substances

  • Antibodies
  • Concanavalin A