Plasma-Derived Exosome Enhances Functional Recovery with Nerve Allograft in the Repair of Segmental Nerve Defect
Tony Chieh-Ting Huang, MD, MSc1, Yicun Wang, MD, PhD2, Guidong Shi, MD3, Jialun Li, MD1, Zeling Long, MD4, Ramona Reisdorf, B.S1, Alexander Y Shin, MD5, Peter C. Amadio, MD6, Atta Behfar, MD, PhD1, Chunfeng Zhao, MD1 and Steven L Moran, MD7, (1)Mayo Clinic, Rochester, MN, (2)Jinlin Hospital, Nanjing, China, (3)Tianjin Medical University, Tianjin, China, (4)The Second Xiangya Hospital, Changsha, China, (5)Orthopaedic Surgery, Div Hand Surgery, Mayo Clinic, Rochester, MN, (6)Orthopaedic Surgery, Mayo Clinic, Rochester, MN, (7)Department of Surgery, Division of Plastic Surgery, Mayo Clinic, Rochester, MN
The treatment of post-traumatic segmental nerve gaps is still challenging. Autologous nerve graft remains the gold standard for segmental peripheral nerve repair as it provides signaling molecules for regeneration, and both cellular and structural support. Unfortunately, nerve autograft is limited due to donor nerve availability and can result in donor site morbidity as well as length and size mismatch. Cell-free nerve allograft is available as an alternative; however, several studies have noted its inferiority to autograft in terms of functional recovery.
Exosome therapy is an emerging field that is being explored for nerve repair. Exosomes are extracellular vesicle released from different cells for intercellular communication and microenvironment homeostasis. In this study, human plasma-derived exosomes were used to accelerate nerve recovery in allograft nerve. We compared exosome-treated nerve allograft to non-treated autograft in nerve regeneration and functional recovery.
Materials & Methods
Plasma-derived exosomes (Rion LLC, Rochester, MN) were tested in cultured Schwann cells to evaluate the effect on proliferation and cell migration. A rat model of sciatic nerve repair was then used evaluate exosomes' effect on nerve regeneration and functional recovery. Exosomes were delivered with Tisseel fibrin sealant acting as the carrier. 3 groups of conditions were tested in 84 Lewis rats: Autograft, Allograft, and Allograft with exosome. Gene expression analysis was done at 7 days post-surgery for nerve regeneration factors. At 12 and 16 weeks, rats were sacrificed for functional evaluation via maximum isometric tetanic force (ITF) and electrophysiological assessment via compound muscle action potential (CMAP). Nerve specimens were then subjected to histological study and immunohistochemistry.
An optimal dosage of 5% exosome mixture was determined in in vitro, which elicited the highest cellular growth and migration. This concentration was applied to the in vivo study. Gene expression analysis demonstrated no statistical significance levels of GAP43, GFAP, CNTF, and s100b between exosome-treated allograft and autograft groups. At both time points, exosome-treated allograft group had comparable functional recovery (CMAP, ITF) as the autograft group, but greater recovery than non-treated allograft group. Upon histological analysis, there were no statistical significant differences between exosome-treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness.
Our results suggested that plasma-derived exosome treatment of decellularized nerve allograft can provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative to the use of nerve autograft.
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