S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Immunosuppressive Effects of Embryonic Stem Cells and Mesenchymal Stem Cells on Allogeneic Skin Graft.
- Han, Kyu Hyun; Cho, Bumrae; Lee, Eun Won; Bang, Ki-Tae; Roh, Han; Ahn, Curie; Yang, Jaeseok; Lee, Han-Kyu
- Issue Date
- WILEY-BLACKWELL PUBLISHING, INC
- AMERICAN JOURNAL OF TRANSPLANTATION; Vol.9 ; 463-463
- Purpose: Both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs)
have immunosuppressive effects. However, there have been confl icting reports
about their impact on transplantation tolerance. Therefore, we tried to elucidate
the immuosuppressive effects of both stem cells on alloimmune response and their
Methods: MSCs were isolated from both C57BL/6 and Balb/C mice and a ESC
cell line originated from C57BL/6 mice were used. Naïve CD4+ T cells and CD11c+
splenic dendritic cells were isolated using MACS system for mixed lymphocyte
reaction. In vitro suppressive activities of both stem cells were tested using CFSE
/7-AAD staining and ELISA technique. To investigate in vivo immunosuppressive
effects of stem cells, either ESCs or MSCs were adoptively transferred via tail vein,
one week before allogeneic skin transplantation.
Results: Both ESCs and MSCs suppressed not only proliferation, but also survival
of CD4+ T cells in mixed lymphocyte reaction. They also suppressed cytokine
production (IL-1b, IL-2, IL-4, IL-10, IL-12, IFN-g and TNF-a). MSCs increased
IL-6 expression, whereas ESCs decreased it. However, there was no change in the
levels of IDO and TGF-b by stem cells. Activation markers such as CD25 and CD44
were downregulated on CD4+ T cells by both stem cells. Transwell experiments
demonstrated that immunosuppression by both stem cells was mainly mediated
by cell to cell contact. Neither ESCs nor MSCs increased foxp3+ regulatory T cell
population. In contrast to their in vitro data, both stem cells failed to prolong skin
graft survival across a major mismatch barrier (Balb/C or DBA/2 to C57BL/6). They
prolonged skin graft survival slightly across minor mismatch barrier(male to female).
Combination therapy of ESCs and anti-CD40L didnot induce skin graft tolerance.
Conclusion: murine ESCs and MSCs suppressed proliferation, survival and cytokine
production of naïve CD4+ T cells in response to in vitro alloimmune stimuli mainly
by cell to cell contact. However, neither ESCs nor MSCs can induce tolerance in
stringent allogeneic skin transplantation models.
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