Enhancing Functional Recovery after Segmental Nerve Defect Using Nerve Allograft Treated with Plasma-Derived Exosome

Author:

Wang Yicun123,Shi Guidong34,Huang Tony C. T.2,Li Jialun25,Long Zeling3,Reisdorf Ramona3,Shin Alexander Y.3,Amadio Peter3,Behfar Atta67,Zhao Chunfeng3,Moran Steven L.2

Affiliation:

1. Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University

2. Division of Plastic Surgery, Department of Surgery

3. Department of Orthopedic Surgery

4. Tianjin Medical University.

5. Department of Plastic Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology

6. Center for Regenerative Medicine

7. Department of Cardiovascular Medicine, Mayo Clinic

Abstract

Background: Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts. Methods: The effect of exosomes on Schwann cell proliferation and migration were evaluated. A rat model of sciatic nerve repair was used to evaluate the effect on nerve regeneration and functional recovery. A fibrin sealant was used as the scaffold for exosome. Eighty-four Lewis rats were divided into autograft, allograft, and allograft with exosome groups. Gene expression of nerve regeneration factors was analyzed on postoperative day 7. At 12 and 16 weeks, rats were subjected to maximum isometric tetanic force and compound muscle action potential. Nerve specimens were then analyzed by means of histology and immunohistochemistry. Results: Exosomes were readily taken up by Schwann cells that resulted in improved Schwann cell viability and migration. The treated allograft group had functional recovery (compound muscle action potential, isometric tetanic force) comparable to that of the autograft group. Similar results were observed in gene expression analysis of nerve regenerating factors. Histologic analysis showed no statistically significant differences between treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness. Conclusions: Plasma-derived exosome treatment of decellularized nerve allograft may provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative for segmental peripheral nerve repair. Clinical Relevance Statement: Off-the-shelf exosomes may improve recovery in nerve allografts.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Surgery

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