Wu Tao, Smith Jay, Nie Hai, Wang Zhen, Erwin Patricia J, van Wijnen Andre J, Qu Wenchun
From the Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota (TW, JS, WQ); Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota (HN, AJvW); Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota (ZW); Medical Library, Mayo Clinic, Rochester, Minnesota (PJE); Division of Pain Medicine, Mayo Clinic, Rochester, Minnesota (WQ); and Spine Center, Mayo Clinic, Rochester, Minnesota (WQ).
Am J Phys Med Rehabil. 2018 Jan;97(1):50-55. doi: 10.1097/PHM.0000000000000837.
Cell therapy based on the trophic, mitogenic, and immunomodulatory capacity of mesenchymal stem cells is a promising treatment modality for degenerative musculoskeletal conditions. Local anesthetics have been commonly used in interventional procedures for alleviating pain, but local anesthetics may have negative impact on MSC dosing because of cytotoxicity or other biological effects. Because previous studies have not reached consensus yet on the potential complications of local anesthetics in cell therapy, we reviewed 11 studies that involve in vitro experimentation with MSCs using aminoamide-type anesthetics including lidocaine, ropivacaine, mepivacaine, bupivacaine, articaine, and prilocaine. Three studies that compare the effects of different types of local anesthetic agents showed that ropivacaine has the least detrimental effects on mesenchymal stem cell populations, whereas lidocaine seems to have the most significant effects on stem cell viability. Concentration- and time-dependent effects on cell viability were reported with bupivacaine, ropivacaine, lidocaine, and mepivacaine. We conclude that local anesthetic agents have time- and concentration-dependent detrimental effects on MSCs. However, in vivo studies will be required to understand the interactions of these agents with MSCs, because in vitro studies cannot replicate the pharmacokinetics of anesthetics in vivo or the recovery of MSCs in a more physiological environment.
基于间充质干细胞的营养、促有丝分裂和免疫调节能力的细胞疗法是治疗退行性肌肉骨骼疾病的一种有前景的治疗方式。局部麻醉剂在介入手术中常用于减轻疼痛,但由于细胞毒性或其他生物学效应,局部麻醉剂可能会对间充质干细胞的剂量产生负面影响。由于先前的研究尚未就局部麻醉剂在细胞治疗中的潜在并发症达成共识,我们回顾了11项涉及使用酰胺类麻醉剂(包括利多卡因、罗哌卡因、甲哌卡因、布比卡因、阿替卡因和丙胺卡因)对间充质干细胞进行体外实验的研究。三项比较不同类型局部麻醉剂效果的研究表明,罗哌卡因对间充质干细胞群体的有害影响最小,而利多卡因似乎对干细胞活力的影响最为显著。布比卡因、罗哌卡因、利多卡因和甲哌卡因对细胞活力的影响具有浓度和时间依赖性。我们得出结论,局部麻醉剂对间充质干细胞具有时间和浓度依赖性的有害影响。然而,由于体外研究无法复制麻醉剂在体内的药代动力学或间充质干细胞在更生理环境中的恢复情况,因此需要进行体内研究以了解这些药物与间充质干细胞的相互作用。