P761: UMBILICAL CORD BLOOD ORIGIN CELLS RECONSTRUCT THE HEMATOPOIESIS OF APLASTIC ANEMIA ANIMAL MODEL

Topic: 11. Bone marrow failure syndromes incl. PNH - Biology & Translational Research Background:Aims: To explore the efficacy and the mechanism of umbilical cord origin cells in combined with cyclosporine A (CsA) in the treatment of aplastic anemia (AA) mouse model. Methods: Immune-mediated AA model mice were treated with CsA+ mesenchymal stem cells (UC-MSC); CsA+ umbilical cord blood regulatory T cells (UCB-Treg); UC-MSC; UCB-Treg; CsA alone or nothing, separately, with 9 mice in each group. CsA was given from the first day of modeling (d0), and cell infusion was given at the same day. Peripheral blood routine test once a week, bone marrow colony culture, bone marrow cell flow cytometry, peripheral blood T cell subsets and serum inflammatory cytokines test at d14 were performed. Transcriptome sequencing was performed for cells from CsA+UC-MSC, CsA+UCB-Treg and CsA group to find the possible related genes. Gene function cluster and signal pathway enrichment analysis were carried out next. Results: Mice transfused with blank control died from pancytopenia within 21 days whereas other mice survived over 28 days. At day 14, WBC count was higher in CsA+UC-MSC and CsA+UCB-Treg groups compared with the other groups(p<0.05). Accordingly, higher BFU and CFU-GM colony count (p<0.01) was found in CsA+UC-MSC and CsA+UCB-Treg groups, and even higher BFU colony count in CsA+UC-MSC group (p<0.01). The highest bone marrow CD34+ cell proportion was in CsA+UC-MSC (9.68±1.35%) and CsA+UCB-Treg group (8.17±0.53%) (p<0.01) as well. TNF-α and IL-2 level in CsA+UC-MSC group (p<0.05) and TNF-α, IL-2 and INF-γ level in CsA+UC-Treg group (p<0.01) were lower compared with CsA group. CsA+UC-MSC had significantly down-regulated histone methylation pathway (p<0.05) whereas CsA+UCB-Treg had significantly up-regulated energy metabolism processes (p<0.05) compared with CsA. Meanwhile, CsA+UC-MSC had up-regulated superoxide dismutase activity compared with CsA+UCB-Treg group. Summary/Conclusion: Adding UC-MSC or UCB-Treg to CsA significantly increased the hematopoiesis reconstruction of AA mice, and UC-MSC was more efficient than UCB-Treg. Adding these cells can further improve the immune abnormalities. CsA+UC-MSC reduced histone methylation pathway and the CsA-UCB-Treg increased energy metabolism processes compared with CsA alone. Keywords: Umbilical cord blood, Mesenchymal stem cell, Regulatory T cell, Aplastic anemia