Abstract
Mesenchymal stromal cells (MSCs) have therapeutic benefits in bleomycin (BLM)-induced pulmonary fibrosis in aged mice that may occur via paracrine factors. Studies suggest that MSC-derived exosomes may act as paracrine effectors. However, whether exosomes can replicate the therapeutic effects of whole-cell MSCs in fibrosis has not been established. We investigated the therapeutic potential of intravenous delivery of MSC-derived exosomes in an established model of BLM-induced pulmonary fibrosis in aged mice. 22 month old C57BL/6 male mice were administered intra-tracheal BLM (2.0 units/kg). Exosomes were isolated from adipose-derived MSCs from young male human and mouse donors. Mice were treated with BLM, BLM + whole-cell human or mouse MSCs, BLM + human or mouse MSC-derived exosomes (n=5/group). Pulmonary fibrosis was assessed at 21-day sacrifice by histology, lung collagen content, expression of TGF-β and Smad2 mRNA, and matrix metalloproteinase-2 (MMP-2) activity. In addition, human skin was used to assess measureable effects on wound healing by human MSC or exosomes. All treatment groups resulted in decreased pulmonary fibrosis compared to BLM only controls (p<0.05), with no difference in fibrotic endpoints between MSC and MSC-derived exosome treatments. In addition, both human MSC and human MSC-derived exosome treatments showed similar efficacy in promoting healing in ex vivo skin wounds. MSC-derived exosomes appear to have similar therapeutic efficacy in BLM-induced pulmonary fibrosis compared to whole-cell MSC infusions. Data support further studies into the potential applications of MSC-derived exosomes in the treatment of fibrotic lung diseases.
- Copyright ©the authors 2017