Seeking stem cell efficacy – immunogenicity matters!

Abstract

Despite hundreds of publications and registered clinical trials, definitive evidence of mesenchymal stem cell (MSC) efficacy does not exist. The notion that mesenchymal stromal cells (MSCs) are immune privileged is changing: MSCs constitutively express MHCI, can be induced to express MHCII and allo-immunization against allogeneic MSCs has been documented. Despite the clinical safety of allo-MSCs, which has been shown exhaustively without evidence for acute rejection reactions or local tissue inflammation, immune recognition and rejection occurs with a reduction in MSC efficacy, we have demonstrated localized tissue inflammation secondary to immune recognition of allo- MSCs. We have also demonstrated localized tissue inflammation secondary to immune recognition of fetal bovine serum contaminants to MSCs. This localized tissue inflammation supports the clinical relevance of allo-recognition of MHC mismatched MSCs and FBS contaminated MSCs, despite the lack of clinically apparent adverse reaction. These findings may explain why definitive proof of MSC efficacy has not been achieved.