Adipose-Derived Stem Cell Modulation of T-Cell Regulation Correlates with Heme Oxgenase-1 Pathway Changes

Ching Ming Chien, Yung Wei Chen, Chien Chang Chen, Yi Chia Wu, Shu Hung Huang, Su Shin Lee, Cheng Sheng Lai, Sin Daw Lin, Ching Jen Wang, Yur Ren Kuo*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations


Background: The authors' previous proteome study revealed that haptoglobin was involved in adipose-derived stem cell modulation of allotransplant survival and T-cell regulation to induce immune tolerance. This study investigated whether adipose-derived stem cells could modulate T-cell regulation through haptoglobin and the downstream heme oxgenase-1 pathway in vitro. Methods: Splenocytes were isolated from Lewis rat spleens and then CD3+ T cells were purified using anti-CD3+ beads. Adipose-derived stem cells were harvested from Lewis rats and co-cultured with the T cells. After Transwell co-culture at different periods, the authors analyzed cell proliferation with a bromodeoxyuridine assay. Cell extractions and culture supernatants were collected for further analysis. Heme oxgenase-1 and related protein expression levels from the adipose-derived stem cells and T cells were detected using Western blotting. The related cytokine expression levels were analyzed with enzyme-linked immunosorbent assay kits. Flow cytometry was used to detect the regulatory T-cell proportion. Results: The adipose-derived stem cells significantly suppressed T-cell proliferation. The regulatory T-cell percentages were significantly increased in the adipose-derived stem cells that were co-cultured with T cells compared with T cells alone without adipose-derived stem cell co-culture. Heme oxgenase-1 expression in concanavalin A-stimulated T cells that were co-cultured with adipose-derived stem cells revealed a significant increase compared with concanavalin A-stimulated T cells alone. Cytokine assays of the culture supernatants revealed that transforming growth factor-β and interleukin-10 were significantly increased and interferon-γ was statistically decreased in the adipose-derived stem cell-co-cultured T-cell group compared with other groups; however, blockade with a heme oxgenase-1 inhibitor (zinc protoporphyrin IX) protected against these changes. Conclusion: Adipose-derived stem cells modulate T-cell proliferation and enhance regulatory T-cell expression, and this correlated with heme oxgenase-1 expression and related cytokine pathway changes.

Original languageEnglish
Pages (from-to)1015-1023
Number of pages9
JournalPlastic and Reconstructive Surgery
Issue number5
StatePublished - 01 11 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2016 by the American Society of Plastic Surgeons.


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