Supplementary Figure 1 A C E B D F ** untreated Anti-miR-375 * * Mtpn Actin B D F ** untreated Stz Stz & siRNA 175 Stz & siRNA 480 Fas Receptor Actin ** * * ** * Supplementary Figure 1

3 passages 10 passages adipocyte osteocyte Supplementary Figure 2

Bright field Fluorescent channel Merge A B C Supplementary Figure 3

Supplementary Figure 4 A B ** ** ** C ** ** ** ** ** PHA+ 500 100 100 PHA+ co-cultured exosomes 200 400 Control PHA PHA+hBMSC exosomes 150 PHA+hBMSCs 75 75 150 300 3.1% 72.0% 62.6% 100 41.4% 34.1% Cell count 50 50 100 200 50 100 25 25 50 102 103 104 105 102 103 104 105 102 103 104 105 102 103 104 105 102 103 104 105 CFSE B ** IL-2 ** IFN-γ ** IL-2sRα C ** ** ** ** ** Supplementary Figure 4

Supplementary Figure 1. Fas and miR-375 silencing improved INS-1E viability and insulin release. (A-B) Fas silencing after siFas treatment was determined by RT-PCR and western blot, *p<0.05, **p<0.01 compared to untreated group. (C-D) INS-1E cell viability and function was evaluated by MTT assay and static insulin release study, *p<0.05, **p<0.01 compared to stz treated group. (E-F) Gene silencing effect of anti-miR-375 and INS-1E cell function was determined by western blot of Mtpn and static insulin release study, *p<0.05, **p<0.01 compared to untreated group. Data was analyzed by Student’s t-test, n=3 Supplementary Figure 2. Differentiation of hBMSC to adipocyte or osteocyte after 10 passages. Supplementary Figure 3. Transfection efficacy of plasmid or siRNA to hBMSC or islet. (A) Transfection efficacy of pshFas-anti-miR-375 to hBMSCs using Xfect transfection reagent. Transfection efficacy of siRNA to human islet using lipofectamine 2000 (B) or Xfect (C) transfection reagent was evaluated under fluorescent microscope. Supplementary Figure 4. hBMSC & PBMC co-cultured exosomes suppressed PBMC proliferation and activation. (A-B) PBMC proliferation were determined by CFSE staining and IL-2, IFNγ, IL-2sRα concentration, **p<0.01 compared to PHA or PHA+hBMSC exosome groups. (C) The immunosuppressive factors including IL-10, VEGF, PGE-2, and TGF-β inside exosomes or medium were measured by ELISA, **p<0.01 concentration of factors in media compared to hBMSC media. Data was analyzed by Student’s t-test, n=3.