Accumulating evidence has elucidated that human mesenchymal stem cells (hMSCs) exert profound analgesic effects on numerous animal models of neuropathic pain, including drug-induced peripheral nerves, diabetes-induced neuropathy, and chronic constriction injury. We aimed to address whether forcing expression of sirtuin 1 (SIRT1) can enhance the efficacy of hMSCs on alleviation of pain sensation. A rat model of chronic constriction injury (CCI) mimicking peripheral nerve injury was incorporated in the study. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) testing were used to measure pain-related behavior. Our results demonstrated that SIRT1 was decreased post-CCI surgery. Compared to hMSCs-control implantation, the hMSCs-SIRT1 (hMSCs overexpressing SIRT1) implantation exhibited superior effects on reducing pro-inflammatory cytokine levels in serum and spinal dorsal horn, while ameliorating neuropathic pain in CCI rat. Engineering hMSCs such as overexpressing SIRT1 may serve as a promising strategy for the treatment of patients with neuropathic pain.

越来越多的证据表明，人类间充质干细胞 (hMSCs) 对多种神经性疼痛动物模型具有深远的镇痛作用，包括药物诱导的周围神经、糖尿病诱导的神经病变和慢性缩窄性损伤。我们旨在解决强制表达 Sirtuin 1 (SIRT1) 是否可以增强 hMSCs 减轻痛觉的功效。模拟周围神经损伤的慢性缩窄性损伤 (CCI) 大鼠模型被纳入研究。缩爪阈值 (PWT) 和缩爪潜伏期 (PWL) 测试用于测量疼痛相关行为。我们的结果表明 SIRT1 在 CCI 手术后降低。与 hMSCs 对照植入相比，hMSCs-SIRT1（过表达 SIRT1 的 hMSCs）植入在降低血清和脊髓背角中的促炎细胞因子水平方面表现出优异的效果，同时改善了 CCI 大鼠的神经性疼痛。工程化 hMSCs，如过表达 SIRT1，可以作为治疗神经性疼痛患者的一种有前景的策略。