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conferenceseries
.com
Volume 8, Issue 3 (Suppl)
J Clin Cell Immunol, an open access journal
ISSN: 2155-9899
Euro Immunology 2017
June 29-July 01, 2017
June 29-July 01, 2017 Madrid, Spain
8
th
European
Immunology Conference
Substitute mesenchymal stromal cells therapy in graft versus host disease with a chemically defined cocktail
Yap Chui Sun, Xiubo Fan, Dian Yang Guo
and
William Ying Khee Hwang
Singapore General Hospital, Singapore
M
esenchymal stromal cell (MSC) therapy has been shown to be effective in phase I/II clinical trials in the treatment of graft versus
host disease (GVHD) after allogeneic hematopoietic cell transplantations. However, MSC trials still face major challenges, such
as complex and time-consuming manipulation, requiring a good manufacturing practice facility, difficult and expensive to produce
etc. In a screen of MSC-derived factors with serial factorial designs, we first time identified two MSC-derived factors, CXCL5 and
CCL24 inhibitor (antibody), which exhibited synergistic immunomodulation effect in mixed lymphocyte reaction. This two-factor
(2F) cocktail also showed excellent
in vivo
immunosuppressive effect in ameliorating GVHD symptoms and improving survival. A
xenograftGVHD animal model was created by injecting 400×106 cells/kg of cryopreserved human PBMCs intoNSGmice respectively.
Four consecutive treatments were given on day-10, day-14, day-17 and day-21 post-transplantation.The 2F cocktail exhibited excellent
immunosuppressive effect as it could improve mice 36-day survival from 19.0% with severe symptoms to 61.9% with mild symptoms
(p<0.01). It was significantly better than BM-MSCs (8.3%, p<0.001) and Cyclosporine A (26.1%, p<0.05). Synergistic effect was again
observed between those two factors (CXCL5, 18.2%; anti-CCL24, 9.1%; p<0.05). The 2F cocktail treatment reduced cytotoxic T
lymphocytes (CTLs), T helper 1 (Th1) cells, Th17 cells, NK cells in the circulation and macrophages in the spleen, but did not affect
human hematopoietic stem cells (HSCs) reconstitution in the bone marrow. Concurrently, it reduced pro-inflammatory cytokine
IFN-γ, IL-1β, IL-6, IL-12, TNF-α, IL-17A, IL-8, MIP-1β and MCP-1 in the circulation. In conclusion, the efficacy of a novel identified
2F cocktail was validated in an
in vivo
xenograft GVHD model. It demonstrated a robust immunosuppressive effect and kept the
development of GVHD under control. The 2F cocktail could be a potential chemically defined substitute for MSCs in GVHD therapy.
Biography
Yap Chui Sun joined the Department of Clinical Translational Research, Singapore General Hospital (SGH) in 2013, and has been working on reprogramming
mesenchymal stem cells. Her first postdoctoral position was at Duke-NUS Medical School, where she was studying the contribution of micro RNAs on thyroid
hormone function. She obtained her Master’s degree in Molecular Immunology at the National University of Singapore and Ph.D. degree in Molecular Oncology
at Brown University (U.S.A.).
yap.chui.sun@sgh.com.sgYap Chui Sun et al., J Clin Cell Immunol 2017, 8:3(Suppl)
DOI: 10.4172/2155-9899-C1-037