Immunogenicity of undifferentiated and differentiated allogeneic mouse mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSC) are multipotential cells with utility in tissue engineering and regenerative medicine. However, the immunological properties and immunogenicity of allogeneic MSC remain poorly defined. Recent studies investigating their immunogenicity remain inconclusive and this has hampered their clinical application. This study investigated the (1) immunogenicity and (2) immunomodulatory properties of bone marrow-derived MSC using an allogeneic mouse model involving Balb/c (responder) and C3H (stimulator) mice. Dermal fibroblasts (DF) were used as controls for cells of mesenchymal origin. Adaptations of the lymphocyte transformation assay (LTA) and mixed lymphocyte reaction (MLR) were used to investigate the immunogenicity and immunomodulatory properties of allogeneic undifferentiated and chondrogenic-differentiated MSC and DF. Both MSC and DF displayed a similar phenotypic profile with the exception of lower expression of CD44 and CD105 in DF. Tri-lineage differentiation of MSC and DF into adipocytes, chondrocytes and osteocytes confirmed their multipotency. In LTA, both undifferentiated and chondrogenic-differentiated allogeneic MSC stimulated lymphocyte proliferation. Allogeneic DF were non-stimulatory but chondrogenic-differentiated DF triggered responder lymphocyte proliferation. In one-way MLR, both allogeneic MSC and DF significantly suppressed Balb/c lymphocyte proliferation. The current challenges in distinguishing between MSC and fibroblasts were apparent throughout the work. These findings support the notion that although MSC possess immunosuppressive properties, they may not be immunoprivileged. Thus, clinical application of allogeneic MSC should be taken with due consideration of their potential immunogenicity.