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MSC-derived Exosomes Promote Bone Fracture Repair

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Review of “Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model” from Stem Cells Translational Medicine by Stuart P. Atkinson

The secretion of paracrine-acting factors influences the success (or failure) of mesenchymal stem cell (MSC)-based bone fracture repair therapies [1]. Exosomes, small cell-derived vesicles, represent one such factor secreted by MSCs and studies from the laboratory of Taisuke Furuta (Hiroshima University, Japan) demonstrated that they can promote muscle regeneration by enhancing myogenesis and angiogenesis [2]. These findings prompted a new Stem Cells Translational Medicine study assessing the potential for MSC-derived exosomes as a novel means to promote bone fracture healing in a mouse model [3].

Initial studies compared MSCs derived from two different mouse strains; wild-type (WT) mice and knockout mice (CD9 KO) known to secrete a reduced number of exosomes [4, 5]. Interestingly, the lack of exosome release in CD9 KO-MSCs correlated to a decrease in bone fracture healing capacity; although treatment with exosomes derived from WT-MSCs permitted the recovery of this lost function.

But what is special about these exosomes? Surprisingly, WT-MSC-derived exosomes were not laden with the expected cargo of pro-fracture healing cytokines (e.g. MCP-1, MCP-3, and SCF1) and instead microRNA analysis demonstrated the overexpression of several species (including miR-338-3p and miR-548aa) suggesting that MSC-derived exosomal microRNAs may be the paracrine-acting factors of importance in bone fracture repair.

So what are the targets for these microRNAs and just do they boost bone fracture repair? Hopefully more studies concerning the regenerative potential of MSC-derived exosomes and distinct microRNA species are in the pipeline; so stay tuned to the Stem Cell Portal to find out more!

References

  1. Liang X, Ding Y, Zhang Y, et al. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant 2014;23:1045-1059.
  2. Nakamura Y, Miyaki S, Ishitobi H, et al. Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration. FEBS Lett 2015;589:1257-1265.
  3. Furuta T, Miyaki S, Ishitobi H, et al. Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model. Stem Cells Translational Medicine 2016;5:1620-1630.
  4. Miyado K, Yoshida K, Yamagata K, et al. The fusing ability of sperm is bestowed by CD9-containing vesicles released from eggs in mice. Proc Natl Acad Sci U S A 2008;105:12921-12926.
  5. Chairoungdua A, Smith DL, Pochard P, et al. Exosome release of beta-catenin: a novel mechanism that antagonizes Wnt signaling. J Cell Biol 2010;190:1079-1091.