Immunogenicity of allogeneic mesenchymal stromal cells: what has been seen in vitro and in vivo?

Mesenchymal stromal cells (MSC) are promising candidates for supporting regeneration and suppressing undesired immune reactivity. Although autologous MSC have been most commonly used for clinical trials, data on application of allogeneic MHC-unmatched MSC were reported. The usage of MSC as an 'off-the-shelf' product would have several advantages; however, it is an immunological challenge. The preclinical studies on the (non)immunogenicity of MSC are contradictory and, unfortunately, solid data from clinical trials are missing. Induction of an alloresponse would be a major limitation for the application of allogeneic MSC. Here we discuss the key elements for the induction of an alloresponse and targets of immunomodulation by MSC as well as preclinical and clinical hints on allo(non)response to MSC.