Schweizer Riccardo, Schnider Jonas T, Fanzio Paolo M, Tsuji Wakako, Kostereva Nataliya, Solari Mario G, Plock Jan A, Gorantla Vijay S
Department of Plastic Surgery, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pa.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa.
Plast Reconstr Surg Glob Open. 2020 Jul 21;8(7):e2953. doi: 10.1097/GOX.0000000000002953. eCollection 2020 Jul.
Regardless of etiology, peripheral nerve injuries (PNI) result in disruption/loss of neuromuscular junctions, target muscle denervation, and poor sensorimotor outcomes with associated pain and disability. Adipose-derived stem cells (ASCs) have shown promise in neuroregeneration. However, there is a paucity of objective assessments reflective of functional neuroregeneration in experimental PNI. Here, we use a multimodal, static, and dynamic approach to evaluate functional outcomes after ASC therapy in a rodent PNI model.
Lewis rats were divided into 3 groups: 10 mm sciatic nerve resection ("CUT" group; n = 10), transection and repair ("REP" group; n = 10), transection and repair plus single-dose ASCs ("ASC" group; n = 12). Allogeneic (Brown Norway rat) ASCs (1 × 10) were administered intravenously on postoperative day 1. Functional outcome was assessed by static sciatic index, toe spread factor, and a dynamic swim test on a weekly basis for 6 weeks. Sciatic nerves and gastrocnemius muscles were harvested at endpoint (6 weeks) for histological analysis.
The ASC group showed accelerated functional recovery on the swim test at 2 weeks postoperatively, with continued improvement over 4 weeks, culminating in superior overall outcomes at 6 weeks compared with the REP group. The CUT group showed no significant improvement from baseline. Nerve histomorphometry correlated well with the swim test results in the ASC group. Gastrocnemius muscle weights showed no difference between the REP and the ASC groups.
Our study confirms that early, single dose, systemic administration of ASC after PNI accelerates and enhances overall motor recovery on static and dynamic functional tests as evidenced by improvements in voluntary as well as involuntary motions.
无论病因如何,周围神经损伤(PNI)都会导致神经肌肉接头的破坏/丧失、靶肌肉失神经支配,以及伴有疼痛和残疾的不良感觉运动结果。脂肪来源干细胞(ASC)在神经再生方面已显示出前景。然而,在实验性PNI中,缺乏反映功能性神经再生的客观评估。在此,我们采用多模态、静态和动态方法来评估啮齿动物PNI模型中ASC治疗后的功能结果。
将Lewis大鼠分为3组:10毫米坐骨神经切除组(“切断”组;n = 10)、横断并修复组(“修复”组;n = 10)、横断并修复加单剂量ASC组(“ASC”组;n = 12)。在术后第1天静脉注射同种异体(棕色挪威大鼠)ASC(1×10)。每周通过静态坐骨神经指数、趾展因子和动态游泳试验评估功能结果,持续6周。在终点(6周)时采集坐骨神经和腓肠肌进行组织学分析。
ASC组在术后2周的游泳试验中显示功能恢复加速,在4周内持续改善,与修复组相比,在6周时总体结果更佳。切断组与基线相比无显著改善。ASC组的神经组织形态计量学与游泳试验结果相关性良好。腓肠肌重量在修复组和ASC组之间无差异。
我们的研究证实,PNI后早期、单剂量、全身给予ASC可加速并增强静态和动态功能测试中的总体运动恢复,自愿和非自愿运动的改善证明了这一点。