Mesenchymal stromal cells in clinical kidney transplantation: how tolerant can it be?

Progress in the improvement of short-term and long-term outcomes of kidney transplantation seems to have reached a plateau, partially due to consequences of very efficient, but nonspecific immunosuppressive drugs. In recent years, various forms of cell therapy, including the use of mesenchymal stromal cells, have been put forward as an alternative strategy for more defined therapy. It is thought that these therapies will not only allow controlled tapering of immunosuppressive medication, but might bring us also closer to the ambition of generating donor-specific immune regulation and tolerance.

Different forms of alloimmunity, including direct, indirect and semi-direct alloantigen presentation have to be controlled before donor-specific immune regulation can be reached. Several mechanisms have been described how mesenchymal stromal cells can affect alloimmunity. Especially, the interaction with professional antigen presenting cells, like dendritic cells, is of critical importance.

This review will discuss the current status of ongoing clinical trials with mesenchymal stromal cells in kidney transplantation and specifically concentrate on the possibilities and impossibilities of how these therapeutic strategies can contribute to control of the different forms of alloreactivity operation in organ transplantation.