In our study we found that human bone marrow-derived mesenchymal stem cells (BM-MSCs) are relatively inefficient in attenuating mortality in a model of fulminant liver failure when compared with human liver-derived stem cells (HLSCs), a liver resident form of MSCs. We did not explore the reason for this difference. Dong et al. suggest that natural killer (NK) cells may limit survival of human BM-MSCs in severe combined immune deficiency (SCID) mice. The interactions between MSCs and NK cells are bivalent.[2-4] In fact, NK cells are capable of killing MSCs only when previously activated. By contrast, MSCs can inhibit interleukin (IL)-2 induced NK cell proliferation and activation.[2-4] The state of NK cell activation in vivo in our experimental setting has not been explored. However, comparing in vitro the sensitivity to NK cells of the BM-MSCs with that of HLSCs we found that IL-15-activated NK cells killed about 30% of BM-MSCs, whereas NK cells were totally ineffective in killing HLSCs (article in preparation). It could be that this insensitivity to NK cells may account for the greater efficiency of HLSCs in the rescue of fulminant liver failure when compared to that of BM-MSCs. However, it should be noted that in our study the conditioned medium of HLSCs reproduced the protective effects of the cells, whereas the conditioned medium of BM-MSCs was totally ineffective. This suggests that the difference in the effects of soluble mediators released from the two cell types could be the primary cause for the different effect of HLSCs and BM-MSCs.
Stefania Bruno, Ph.D.1
Ciro Tetta, M.D.2
Giovanni Camussi, M.D.3
1Department of Molecular Biotechnology and Health Sciences, Bad Homburg, Germany
2Translational Center for Regenerative Medicine, Fresenius Medical Care, Bad Homburg, Germany
3Department of Medical Sciences, University of Torino, Torino, Italy