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Supplemental Figure Legends Supplemental Figure 1. Antibody array analysis of conditioned media from endothelial cells after treatment with exosomes (*p <.5 and **p =.6). The control media is media that has not been exposed to cells (Media), the control group (Ctrl) is conditioned media from untreated cells and the exosome group (Exo) is conditioned media from cell treated with exosomes. This information has now been included in the figure legend. Supplemental Figure 2. Fibroblasts were treated with 1-methyl-3-nitro-1-nitrosoguanidine for three days. The cells were then treated with exosomes for two weeks at the indicated concentrations and then tested for colony formation in a soft agar assay. Supplemental Figure 3. Release kinetics of exosomes from alginate beads. Alginate gels were loaded with exosomes at the same concentration used for the in vivo studies and incubated at 37 C in PBS. The supernatant was collected at specific time points and assayed for exosome concentration using a CD63 ELISA. Page 24 of 34

Supplemental Figure 1 16 14 12 8 6 4 2 Activin A 14 12 8 6 4 2 ADAMTS-1 25 15 5 Angiogenin 3 25 15 5 Angiopoietin-1 18 16 14 1 8 6 4 Angiopoietin-2 ** 3 25 15 5 9 8 7 6 5 4 3 2 1 Amphiregulin 8 7 6 5 4 3 2 1 Artemin 3 16 25 14 12 15 8 6 4 5 2 Coagulation Factor III 3 4 35 25 3 25 15 15 5 5 CXCL16 3 25 15 5 14 3 1 25 8 15 6 4 5 3 12 DPPIV Endothelin-1 Media Control Ctrl Exo No Exo Exo GDNF 3 8 7 25 6 5 15 4 3 2 5 1 3 6 25 5 4 15 3 5 25 3 EGF FGF acidic GM-CSF 3 18 25 16 14 12 15 8 6 5 4 2 3 16 25 14 12 15 8 6 4 5 2 8 3 EG-VEGF FGF basic HB-EGF Endoglin 16 3 14 25 1 15 8 6 4 5 FGF-4 3 9 25 8 7 6 15 4 3 2 5 1 HGF 3 14 3 18 16 25 14 1 15 8 6 4 5 7 3 6 25 5 4 15 3 5 7 3 Endostatin Control Media Exo Ctrl No Exo FGF-7 IGFBP-1 25 8 15 6 4 5 2 25 15 15 5 5 7 25 6 5 4 15 3 5 25 12 8 15 6 4 5 2 Exo 6 25 5 4 15 3 5 25 3 25 15 15 5 3 16 14 25 12 15 8 6 4 5 2 3 4 35 25 3 25 15 15 5 5 9 3 8 25 7 6 5 15 4 3 5 IGFBP-2 Leptin ** NRG1-beta1 Persephin 3 6 25 5 4 15 3 5 7 3 6 25 5 4 15 3 5 4 3 35 25 3 25 15 15 5 5 3 18 25 16 14 12 15 8 6 5 4 2 IGFBP-3 MCP-1 Pentraxin 3 Platelet Factor 4 IL-1beta 35 3 3 25 25 15 15 5 MIP-1a 3 14 25 12 8 15 6 4 5 2 PD-ECGF 3 6 25 5 4 15 3 5 PlGF 3 14 25 1 8 15 6 4 5 Page 25 of 34 5 3 45 25 4 35 3 25 15 15 5 5 3 18 16 25 14 12 15 8 6 4 5 2 3 9 25 8 7 6 15 5 4 3 5 14 3 1 25 8 15 6 4 5 IL-8 MMP-8 PDGF-AA Prolactin * 3 4 25 35 3 25 15 15 5 5 3 25 15 5 3 9 25 8 7 6 15 5 4 3 5 3 25 25 15 15 5 LAP (TGF-beta1) MMP-9 PDGF-AB/PDGF-BB Serpin B5

Supplemental Figure 1 (con t) 3 9 8 25 7 6 5 15 4 3 5 16 3 14 25 1 15 8 6 4 5 4 3 35 25 3 25 15 15 5 5 Persephin Serpin E1 Thrombospondin-2 3 18 25 16 14 12 15 8 6 5 4 2 3 25 15 5 35 3 3 25 25 15 15 5 Platelet Factor 4 Serpin F1 upa 14 3 1 25 8 15 6 4 5 8 3 7 25 6 5 4 15 3 5 16 3 14 25 12 15 8 6 4 5 2 PlGF TIMP-1 Vasohibin 14 3 1 25 8 15 6 4 5 3 8 25 7 6 5 15 4 3 5 3 14 25 12 8 15 6 4 5 2 Prolactin TIMP-4 VEGF 3 25 25 15 15 5 3 9 25 8 7 6 15 5 4 3 5 3 25 15 5 Serpin B5 Thrombospondin-1 VEGF-C Page 26 of 34

Supplemental Figure 2 No Treatment 4.4x1 8 exo/ml 3x1 8 exo/ml Page 27 of 34

Supplemental Figure 3 12% Cumulative Exosome Release % 8% 6% 4% 2% % 1 2 3 4 5 6 7 8 9 1 11 12 13 Time (Days) Page 28 of 34