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[X. Stem cell biology-5]



                        Immunomodulatory effect and maintenance of


                       differentiation via PD1/PDL-1 axis in osteoblasts


                                     differentiated from hADMSCs



                                 Seung-Cheol Lee¹, Min Kyoung Shin¹, Jung-Suk Sung¹˙*


                      ¹Department of Life Science, Dongguk University-Seoul, Goyang 10326, South Korea





        Human adipose tissue derived mesenchymal stem cells (hADMSCs) are promising candidate in stem cell therapy.
        However the improved immunomodulatory effect and efficacy on differentiation potential are required to pass over
        limitation  of the therapy.  Recent studies reported  that  MSCs  secrete  PD-L1  mediating  T  cell  mediated

        immunosuppression. In this study, we showed that the expression level of Programmed cell death protein 1 (PD-1),
        was  increased  in  the  osteoblasts  when  compared  with  hADMSCs.  Interestingly,  the  expression  levels  of  pro-

        inflammatory cytokines (IL-6, TNF-α, IL-1β) were decreased in differentiated osteoblasts co-cultured with hADMSCs,
        attenuating the expression levels by PD1/PD-L1 pathway inhibition. IL-6 induction mediated by TNF-α and IL-1β is

        known for effect on promoting osteoclastogenesis in osteoblasts. We showed that osteoblasts co-cultured with
        hADMSCs  expressed  higher  levels  of  osteogenic  markers  (RUNX2,  OCN,  ALP)  compared  with  non-co-cultured

        osteoblasts. We suggest here that PD1/PDL-1 axis mediates inhibition of pro-inflammatory cytokine expressions
        and  osteoclastogenesis  in  osteoblasts  co-cultured  with  hADMSCs.  [This  work  was  supported  by  the  National

        Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2017R1D1A1B03030983)]
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