Mochamad Syaifudin (2021) ##### PATEN ##### Respon Graft Versus Host Disease (GvHD) Pada Kokultivasi Sel Punca Mesenkimal Tali Pusat Dan Sel Punca Hematopoitik Cd34+ Darah Tepi Talasemia Mayor (Penelitian Eksperimental Laboratoris. Disertasi thesis, UNIVERSITAS AIRLANGGA.

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Abstract

Background. The main problem in the implementation of bone marrow transplantation (BMT) in patients with thalassemia major in the world today is graft versus host disease (GvHD). One of the causes is incompatibility of the donor's human leucocyte antigen (HLA) with recipient T lymphocytes. The gene that plays the most role in this GvHD reaction is the donor human leucocyte antigen (HLA), and the HLA which has immunosuppressive properties is the nonclassical class 1b HLA-G. HLA-G is found on the surface of mesenchymal stem cell (MSC) membranes. MSC when activated with T lymphocytes, will secrete immunosuppression molecules, HLA-G and forkhead box protein 3 (Foxp3), and express interleukin-10 (IL-10), transforming growth factor ß (TGFß), prostaglandin E2 (PGE2), and indoleamine-2,3-dioxygenase (IDO). MSC will induce CD34+ hematopoietic stem cells to keep dendritic cells (DC) in immature (iDC) state which will strengthen the inhibition against the proliferation of CD4+ and CD8+ T cells, thereby reducing the GvHD reaction. Methods. The research design was carried out as an experimental pre-posttest only control group design (in-vitro). T lymphocytes cultured from peripheral blood of children with thalassemia major were exposed to MSC and CD34+ hematopoietic stem cells from sibling donor. The experimental unit was divided into 4 groups: (1) The positive control group, untreated T lymphocytes, (2) T lymphocytes exposed to MSC, (3) T lymphocytes exposed to CD34+ hematopoietic stem cells, (4) T lymphocytes exposed to co-cultivation of MSC-CD34+. Elisa examination of IL-10, TGFß, PGE2, IDO secretion and immunocytochemistry examination of the expression of HLA-G, Foxp3, CD4+, and CD8+ were done at 0, 12, and 24 hours incubation time. Results. Co-cultivation of MSC-CD34+ stem cells in T lymphocyte culture was able to increase the secretion of IL-10, TGFß, PGE2, IDO, HLA-G and Foxp3 significantly (p <0.05) at 12 and 24 hours. CD34+ hematopoietic stem cells and MSC-CD34+ stem cell co-cultivation were able to significantly reduce CD4+ expression (p <0.05) at 12 and 24 hours. Furthermore, MSC and MSCCD34+ stem cell co-cultivation were able to reduce CD8+ expression significantly (p <0.05) at 24 hours. Conclusions. Co-cultivation of MSC-CD34+ hematopoietic stem cells in T lymphocyte culture was able to reduce the GvHD reaction.

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