TY - JOUR
T1 - The CD45+ fraction in murine adipose tissue derived stromal cells harbors immune-inhibitory inflammatory cells
AU - Nasti, Alessandro
AU - Sakai, Yoshio
AU - Seki, Akihiro
AU - Buffa, Geraldine Belen
AU - Komura, Takuya
AU - Mochida, Hatsune
AU - Yamato, Masatoshi
AU - Yoshida, Keiko
AU - Ho, Tuyen T.B.
AU - Takamura, Masayuki
AU - Usui, Soichiro
AU - Wada, Takashi
AU - Honda, Masao
AU - Kaneko, Shuichi
N1 - Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/12
Y1 - 2017/12
N2 - Stromal cells in adipose tissue are useful for repair/regenerative therapy as they harbor a substantial number of mesenchymal stem cells; therefore, freshly isolated autologous uncultured adipose tissue derived stromal cells (u-ADSCs) are useful for regenerative therapy, and obviate the need for mesenchymal stem cells. We evaluated the therapeutic effect of murine u-ADSCs and sorted subsets of u-ADSCs in a concanavalin A (ConA) induced murine model of hepatitis, as well as their characteristics. We found that 10–20% of u-ADSCs expressed the CD45 leukocyte-related antigen. CD68, which is a marker of macrophages (MΦs), was expressed by 50% of CD45+ u-ADSCs. About 90% of CD68+CD45+ cells expressed CD206 antigen, which is a marker of inhibitory M2-type MΦs. Genes related to M2-type MUs were especially more highly expressed by CD45+CD206+ u-ADSCs than by CD45− u-ADSCs. CD45+ u-ADSCs inhibited the expression of cytokines/chemokines and suppressed the proliferation of splenocytes stimulated with ConA. We observed that not only whole u-ADSCs, but also the CD45+ subset of u-ADSCs ameliorated the ConA-induced hepatitis in mice. In conclusion, we show that freshly isolated murine u-ADSCs were effective against acute hepatitis, and CD45+ u-ADSCs acting phenotypically and functionally like M2-type MΦs, contributed to the repair of liver tissue undergoing inflammation.
AB - Stromal cells in adipose tissue are useful for repair/regenerative therapy as they harbor a substantial number of mesenchymal stem cells; therefore, freshly isolated autologous uncultured adipose tissue derived stromal cells (u-ADSCs) are useful for regenerative therapy, and obviate the need for mesenchymal stem cells. We evaluated the therapeutic effect of murine u-ADSCs and sorted subsets of u-ADSCs in a concanavalin A (ConA) induced murine model of hepatitis, as well as their characteristics. We found that 10–20% of u-ADSCs expressed the CD45 leukocyte-related antigen. CD68, which is a marker of macrophages (MΦs), was expressed by 50% of CD45+ u-ADSCs. About 90% of CD68+CD45+ cells expressed CD206 antigen, which is a marker of inhibitory M2-type MΦs. Genes related to M2-type MUs were especially more highly expressed by CD45+CD206+ u-ADSCs than by CD45− u-ADSCs. CD45+ u-ADSCs inhibited the expression of cytokines/chemokines and suppressed the proliferation of splenocytes stimulated with ConA. We observed that not only whole u-ADSCs, but also the CD45+ subset of u-ADSCs ameliorated the ConA-induced hepatitis in mice. In conclusion, we show that freshly isolated murine u-ADSCs were effective against acute hepatitis, and CD45+ u-ADSCs acting phenotypically and functionally like M2-type MΦs, contributed to the repair of liver tissue undergoing inflammation.
KW - Adipose tissue
KW - ConA hepatitis
KW - Macrophages
KW - Repair/regenerative therapy
KW - Stromal cells
UR - http://www.scopus.com/inward/record.url?scp=85037559542&partnerID=8YFLogxK
U2 - 10.1002/eji.201646835
DO - 10.1002/eji.201646835
M3 - Article
C2 - 28891216
AN - SCOPUS:85037559542
SN - 0014-2980
VL - 47
SP - 2163
EP - 2174
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -