Stem cell secretome attenuates acute rejection in rat lung allotransplant

OBJECTIVES: Stem cells secrete significant amounts of bioactive factors in their secretome that can be immunosuppressive. We studied the effect of the secretome obtained from bone marrow-derived mesenchymal stem cells (BMSC-sec) in combination with cyclosporine A following acute rejection of lung allografts in the rat. METHODS: Lung allotransplants were performed from male Brown Norway donor rats to recipient male Fisher 344 rats. Rat BMSC-sec was introduced intratracheally in the recipient every day after the transplant until the day the animal was sacrificed. Group A (n = 5) received control medium and cyclosporine A (2.5 mg/kg body weight intraperitoneally) for 5 days post-transplant and group B (n= 5) received BMSC-sec and cyclosporine A. Blood gas analysis was performed to assess graft function at day 5 only from the graft, and the tissue was sampled for measurement of the wet/dry ratio and histological grading of rejection. RESULTS: All control animals (group A) showed severe signs of rejection. At day 5 grafts in group B showed improved gas exchange (i.e. mean PaO2 mmHg 237.9 +/- 130mmHg vs 24.9 +/- 7.8mmHg in group A). Histological examination according to the International Society of Heart and Lung Transplantation (ISHLT) revealed moderate to severe rejection in all animals in group A (III B) and a significant improvement in group B (I-IIA). The wet/dry ratio was also reduced in group B to 6.19 +/- 0.6 compared to 9.36 +/- 2 in group A. Furthermore, in vitro T-cell proliferation was reduced after treatment with BMSC-sec for CD 3 cells (69.55 +/- 07 vs 73 +/- 0.84), for CD 4 (24.95 +/- 1.2 vs 27.75 +/- 0.21) and for CD 8 cells (3.75 +/- 0.2 vs 5.68 +/- 0.02). CONCLUSIONS: The BMSC-sec is a promising novel cell-based therapeutic option for acute rejection in a rat lung allograft model.