Abstract
AbstractPurpose Glucocorticoid treatment of ex‐vivo generated donor bone marrow derived dendritic cells (BMDCs) will promote graft survival upon injection into corneal transplant recipients.Methods BMDCs were propagated from Dark Agouti (DA) rat BM precursor cells and for glucocorticoid treated BMDCs, dexamethasone (Dexa) 10e‐6M was added to the culture. BMDCs +/‐ Dexa phenotype, APC function and immunostimulatory capacity were examined. A fully allogeneic rat corneal transplantation model (DA to LEW) was used for in‐vivo studies. BMDCs +/‐ Dexa were harvested and 1x10e6 cells injected intravenously into recipients 7 days prior to corneal transplantation. Graft survival and development of opacity, edema and neovascularisation were monitored. On the average day of rejection graft infiltrating cell populations were analysed.Results Ex‐vivo generated BMDCs have a semi‐mature phenotype and can be treated with Dexa to maintain their immature phenotype (n=5 p<0.05). BMDCs are capable of activating allogeneic lymphocytes, efficiently presenting antigen and activating antigen specific T cells however, there is a reduction in the level of proliferation (n=4, p<0.05). When applied in‐vivo BMDCs and Dexa BMDCs significantly prolong corneal allograft survival (MST> 30d, n=14 p<0.0004 and n=24 p<0.0001 resp.) compared to untreated allogeneic controls (MST 18d, n=11). A significant reduction in the total number of graft infiltrating cells was observed for both treated groups (p<0.05).Conclusion Our results demonstrate a significant therapeutic effect of donor‐derived BMDCs with and without glucocorticoid treatment to prolong corneal transplant survival which represents a novel therapeutic approach for the prevention of corneal allograft rejection.
Published Version
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