Efficacy of adipose-derived stem cells in preventing peripheral nerve adhesion and promoting nerve regeneration: A laboratory investigation in a rat model

Yuta Nakamura; Kaoru Tada; Mika Akahane; Tsuyoshi Hattori; Masashi Matsuta; Atsuro Murai; Soichiro Honda; Osamu Hori; Satoru Demura

doi:10.1016/j.jos.2024.09.005

Efficacy of adipose-derived stem cells in preventing peripheral nerve adhesion and promoting nerve regeneration: A laboratory investigation in a rat model

J Orthop Sci. 2024 Oct 7:S0949-2658(24)00187-8. doi: 10.1016/j.jos.2024.09.005. Online ahead of print.

Authors

Yuta Nakamura¹, Kaoru Tada², Mika Akahane¹, Tsuyoshi Hattori³, Masashi Matsuta¹, Atsuro Murai¹, Soichiro Honda¹, Osamu Hori³, Satoru Demura¹

Affiliations

¹ Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
² Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan. Electronic address: tdkr@med.kanazawa-u.ac.jp.
³ Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.

PMID: 39379214
DOI: 10.1016/j.jos.2024.09.005

Abstract

Background: Neurolysis alone or administration of anti-adhesion products after neurolysis is performed to treat peripheral nerve adhesion; however, the recovery of nerve function is poor. This study aimed to investigate the efficacy of adipose-derived stem cells (ADSCs) for peripheral nerve adhesion in a rat model.

Methods: As a nerve adhesion procedure, the neural bed was coagulated, and the epineurium of the sciatic nerve was sutured to the coagulated neural bed using nylon. Neurolysis was performed 6 weeks after the nerve adhesion procedure, and saline (control group) or ADSCs (ADSC group) were administered around the nerve where neurolysis was performed. Evaluations were performed 6 weeks after the administration.

Results: The wet weight ratio of the tibialis anterior muscle and nerve conduction velocity, which are indicators of nerve regeneration, were significantly better, while tensile strength, which is an indicator of the severity of nerve adhesion, was significantly lower in the ADSC group than in the control group. In the nerve, the expression of interleukin-10 and transforming growth factor-β in the nerve was significantly higher and that of tumor necrosis factor-α was significantly lower in the ADSC group than in the control group. Furthermore, significantly fewer M1 macrophages and significantly more M2 macrophages were observed in the ADSC group than in the control group. In the perineural scar, significantly fewer perineural collagen fibers and significantly more vascularization were observed in the ADSC group than in the control group.

Conclusions: ADSCs prevented peripheral nerve adhesion by reducing perineural scarring and enhancing vascularization. Additionally, ADSCs promoted nerve regeneration by decreasing inflammatory cytokine levels and increasing anti-inflammatory cytokine levels, as ADSCs regulated macrophage polarization from M1 to M2 macrophages. These findings hold promise for using ADSCs to treat nerve adhesion.

Keywords: Adipose-derived stem cell; Nerve regeneration; Peripheral nerve adhesion; Prevention of adhesion.