Bootcongres

Introduction Mesenchymal Stromal Cells (MSC) are emerging as treatment for various diseases due to their immune modulatory and reparative properties. Studies with MSC as induction therapy and in transplant recipients with subclinical rejection and fibrosis demonstrated that treatment with MSC is safe and clinically feasible. Further, they indicated immune suppression in a clinical setting. MSC are commonly isolated from Bone Marrow (BM). However, Adipose tissue (AT) is another important source of MSC which is easier to access. In the present study we compared the immune suppressive capacities of BM-MSC and A-MSC in vitro and in an in vivo transplantation model.

Methods Human BM-MSC (n=5) and AT-MSC (n=5) were isolated from healthy individuals. Gene expression by unstimulated and IFNγ stimulated BM-MSC and AT-MSC were evaluated using PCR. Further, inhibition of αCD3αCD28 activated PBMC proliferation by IFNγ stimulated MSC of both origins was compared. Finally, we compared the in vivo anti-rejection effect of BM-MSC and AT-MSC in a humanized mouse system. SCID mice were transplanted with human skin grafts and injected with human allogeneic PBMC and IFNγ treated BM-MSC (n=8) or AT-MSCs (n=7). Effect of MSC on skin graft rejection was studied. 

Results CXCL-10 and IDO expression was markedly increased upon IFNγ stimulation of BM-MSC and AT-MSC. Stimulated BM-MSC and AT-MSC had a similar capacity to inhibit the proliferation of activated PBMC in a dose dependent manner. Injection of human allogeneic PBMC in SCID mice bearing human skin grafts, resulted in pronounced CD45+ T-cell infiltrates and increased IFNγ expression in the skin grafts which was markedly inhibited by both BM-MSC and AT-MSCs. 

Conclusion Direct comparison of BM-MSC and A-MSC shows their comparable capacity to inhibit immune responses in vitro as well as to downregulate alloreactivity in vivo. Finally, the humanized character of our in vivo study highlights the clinical potential of MSC.