Exosomes Are Comparable to Source Adipose Stem Cells in Fat Graft Retention with Up-Regulating Early Inflammation and Angiogenesis

Background: Exosomes derived from mesenchymal stem cells possess functional properties similar to those of their parent cells, suggesting that they could play a pivotal role in tissue repair and regeneration. Methods: Using lipotransfer as a surrogate, exosomes were isolated from mouse adipose-derived stem cell-conditioned medium and characterized. Minced fat tissue mixed with exosomes, source cells (cell-assisted lipotransfer), or saline was implanted subcutaneously in the lower back of C57/BL mice bilaterally (n = 16 each). Transferred fat tissues were harvested and analyzed at 3 and 10 weeks. Results: At 3 and 10 weeks after the transfer, fat grafts in groups of exosomes and cell-assisted lipotransfer showed better fat integrity, fewer oil cysts, and reduced fibrosis. At week 10, graft retention rates in cell-assisted lipotransfer (50.9 +/- 2.4 percent; p = 0.03) and exosome groups (56.4 +/- 1.6 percent; p < 0.001) were significantly higher than in the saline group (40.7 +/- 4.7 percent). Further investigations of macrophage infiltration, inflammatory factors, angiogenic factors, adipogenic factors, and extracellular matrix revealed that those exosomes promoted angiogenesis and up-regulated early inflammation, whereas during mid to late stages of fat grafting, they exerted a proadipogenic effect and also increased collagen synthesis level similarly to their source cells. Conclusions: The adipose-derived stem cell-derived exosomes demonstrated effects comparable to those of their source cells in achieving improved graft retention by up-regulating early inflammation and augmenting angiogenesis. These features may enable exosomes to be an attractive cell-free alternative in therapeutic regenerative medicine.