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Umbilical cord derived mesenchymal stromal cells are attractive candidates for a novel immunosuppressive therapy approach against Graft-versus-Host-Disease after umbilical cord blood transplantation

Aus Nabelschnurblut abgeleitete, mesenchymale Stromazellen sind attraktive Kandidaten für die GvHD-Prävention nach Nabelschnurbluttransplantationen
: Heider, A.

Oncology research and treatment 37 (2014), S.109-110
ISSN: 2296-5270
ISSN: 2296-5262
Deutsche, Österreichische und Schweizerische Gesellschaften für Hämatologie und Medizinische Onkologie (gemeinsame Jahrestagung) <2014, Hamburg>
Konferenzbeitrag, Zeitschriftenaufsatz
Fraunhofer IZI ()

Graft-versus-Host-Disease (GvHD) is one of the major complication following allogeneic hematopoietic stem cell transplantations (HSCT). Mesenchymal stromal cells (MSCs) exhibit unique immune-modulating features with the potential to suppress GvHD. Here, we have investigated the ability of umbilical cord-derived MSCs (UC-MSCs) to control a GvHD-like reaction both in vitro using mixed-lymphocyte reactions (MLRs) and in vivo using a NOD/SCID/IL2Rcγnull (NSG) mouse model. Methods: Firstly, the MLRs were adapted to establish a robust immune reaction between umbilical cord blood-derived mononuclear cells (UCB-MNCs) from two immune-incompatible donors that was comparable to those seen with peripheral blood mononuclear cells (PBMCs). The effects of varying doses of UC-MSCs and bone marrow-derived MSCs (BM-MSCs) on 3H-thymidine incorporation were then compared. Secondly, UCB-MNCs were used to induce a GvHD-like reaction in NSG mice, and the effects of UC-MSCs on engraftment and GvHD were determined. Both allogeneic and syngeneic combinations of UCB-MNCs and UC-MSCs were used. The mice were monitored over 54 days for weight, GvHD symptoms, by flow cytometry and full blood cell counts as well as final histology.Results: A robust MLR reaction using UCB-MNCs was achieved by cytokine stimulation. Both BM-MSC and UC-MSC had similar effects on the MLR reaction, but these in vitro effects of MSC ranged from suppression to activation of the immune reaction in a donor/batch dependent manner.The results in NSG mice showed that a number of 1.75·107 UCB-MNCs was sufficient to induce a measureable GvHD-like reaction while maintaining survival in most cases. Freshly isolated UC-MSCs were given in different doses (5·104 and 1·106) on day 0 or day 14 following UCB-MNC injection. The administration of 5·104 syngeneic MSC at day 0 led to a significant higher survival rate compared to the controls. Flow cytometric analysis revealed a significant decrease in both human CD8+ cells and CD45 chimerism after administration of 1·106 MSC, with a higher decrease in a syngeneic setting. Qualitative histological analyses confirmed GvHD in the skin and intestine of control animals that was reduced to a minimum in MSC-treated animals.Conclusions: We have established a model system of GvHD using UCB-MNCs and an in vitro assay to test for immune-compatibility and -suppression. The in vivo results confirm a suppression of GvHD by UC-MSC.