Errante Emily L, Tigre Joseph Yunga, Schaeffer Ericka A, Costello Meredith C, Kloehn Andrew J, Puerto Aiko, Khan Aisha, Pressman Yelena, Silvera Risset, Sanchez Francisco J, Noga Brian R, Dietrich W Dalton, Levi Allan D, Burks S Shelby
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
PLoS One. 2025 Jan 7;20(1):e0313292. doi: 10.1371/journal.pone.0313292. eCollection 2025.
Peripheral nerve injury (PNI) is characterized by a loss of cellular and axonal integrity, often leading to limited functional recovery and pain. Many PNIs are not amenable to repair with traditional techniques; however, cell therapies, particularly Schwann cells (SCs), offer the promise of neural tissue replacement and functional improvement. Exosomes, which carry cellular signaling molecules, can be secreted by SCs and have shown promise in PNI. Our laboratory has had success using SCs in preclinical and clinical treatment settings. Transplanted cells have several known limitations, which exosomes mitigate. To that end, the current study investigated if implanted SC-derived exosomes in conduits, conduits with SCs, reverse autograft, or empty conduits comparably improve axonal regeneration and pain outcomes 16-weeks after repair of a long gap PNI in adult rats. Results show that there were no differences between groups in the von Frey filament testing or in the Hargreaves test. Electrophysiological testing showed a significant difference between the injured (ipsilateral) and uninjured (contralateral) limbs while histological assessment showed a significant difference between axonal counts in different areas of the conduit. Based on the results of the current study, more research is needed to understand the therapeutic role of exosomes in PNI.
周围神经损伤（PNI）的特征是细胞和轴突完整性丧失，常导致功能恢复受限和疼痛。许多周围神经损伤无法用传统技术修复；然而，细胞疗法，尤其是雪旺细胞（SCs），为神经组织替代和功能改善带来了希望。携带细胞信号分子的外泌体可由雪旺细胞分泌，并在周围神经损伤中显示出前景。我们实验室在临床前和临床治疗中使用雪旺细胞取得了成功。移植细胞有几个已知的局限性，外泌体可减轻这些局限性。为此，本研究调查了在成年大鼠长节段周围神经损伤修复16周后，将植入雪旺细胞来源的外泌体置于导管、含雪旺细胞的导管、逆行自体移植或空导管中，是否能同等程度地改善轴突再生和疼痛结果。结果显示，在von Frey细丝测试或哈格里夫斯测试中，各组之间没有差异。电生理测试显示受伤（同侧）和未受伤（对侧）肢体之间存在显著差异，而组织学评估显示导管不同区域的轴突计数之间存在显著差异。基于本研究结果，需要更多研究来了解外泌体在周围神经损伤中的治疗作用。
