Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

Haoshuai Tang; Junjin Li; Hongda Wang; Jie Ren; Han Ding; Jun Shang; Min Wang; Zhijian Wei; Shiqing Feng

doi:10.4103/1673-5374.380911

Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

Neural Regen Res. 2024 Apr;19(4):900-907. doi: 10.4103/1673-5374.380911.

Authors

Haoshuai Tang¹, Junjin Li¹, Hongda Wang¹, Jie Ren¹, Han Ding¹, Jun Shang¹, Min Wang², Zhijian Wei³, Shiqing Feng³

Affiliations

¹ Department of Othopaedics; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.
² Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
³ Department of Othopaedics; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; Department of Othopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Othopedics, Advanced Medical Research Institute; Orthopedic Research Center of Shandong University & Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.

Abstract

Complete transverse injury of peripheral nerves is challenging to treat. Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration. In previous studies, a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration. This three-dimensional (3D) composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly (lactic-co-glycolic acid) tube. However, whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown. In this study, we tested a comprehensive strategy for repairing long-gap (10 mm) peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes. Repair effectiveness was evaluated by sciatic functional index, sciatic nerve compound muscle action potential recording, recovery of muscle mass, measuring the cross-sectional area of the muscle fiber, Masson trichrome staining, and transmission electron microscopy of the regenerated nerve in rats. The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function, similar to autograft transplantation. More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes, which may have contributed to the observed increase in axon regeneration and distal nerve reconnection. Therefore, the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

Keywords: axon growth; collagen; exosome; human umbilical cord mesenchymal stem cells; hyaluronic acid; muscular atrophy; nerve guidance conduits; peripheral nerve regeneration.

Grants and funding

Funding: This study was supported by the National Key Research and Development Project of Stem Cell and Transformation Research, No. 2019YFA0112100 (to SF), the National Natural Science Foundation of China No. 81930070 (to SF), Multi-fund Investment Key Projects, No. 21JCZDJC01100 (to ZW), and the Tianjin Science and Technology Planning Project, No. 22JRRCRC00010 (to SF).