Dorsal root rhizotomy (DRZ) is currently considered an untreatable injury, resulting in the loss of sensitive function and usually leading to neuropathic pain. In this context, we recently proposed a new surgical approach to treat DRZ that uses platelet-rich plasma (PRP) gel to restore the spinal reflex. Success was correlated with the reentry of primary afferents into the spinal cord. Here, aiming to enhance previous results, cell therapy with bioengineered human embryonic stem cells (hESCs) to overexpress fibroblast growth factor 2 (FGF2) was combined with PRP. For these experiments, adult female rats were submitted to a unilateral rhizotomy of the lumbar spinal dorsal roots, which was followed by root repair with PRP gel with or without bioengineered hESCs. One week after DRZ, the spinal cords were processed to evaluate changes in the glial response (GFAP and Iba-1) and excitatory synaptic circuits (VGLUT1) by immunofluorescence. Eight weeks postsurgery, the lumbar intumescences were processed for analysis of the repaired microenvironment by transmission electron microscopy. Spinal reflex recovery was evaluated by the electronic Von Frey method for eight weeks. The transcript levels for human FGF2 were over 37-fold higher in the induced hESCs than in the noninduced and the wildtype counterparts. Altogether, the results indicate that the combination of hESCs with PRP gel promoted substantial and prominent axonal regeneration processes after DRZ. Thus, the repair of dorsal roots, if done appropriately, may be considered an approach to regain sensory-motor function after dorsal root axotomy.

中文翻译：

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背侧根切断术后脊柱反射恢复和富血小板血浆（PRP）凝胶结合生物工程人胚干细胞（hESCs）修复

背根神经根切开术（DRZ）目前被认为是无法治愈的损伤，导致敏感功能丧失，通常导致神经性疼痛。在这种情况下，我们最近提出了一种新的外科治疗DRZ的方法，该方法使用富含血小板的血浆（PRP）凝胶恢复脊柱反射。成功与原发子再进入脊髓有关。在这里，为了增强先前的结果，将生物工程化的人类胚胎干细胞（hESC）过度表达成纤维细胞生长因子2（FGF2）的细胞疗法与PRP结合使用。对于这些实验，成年雌性大鼠接受了腰椎背侧根的单侧根切除术，随后用有或没有生物工程hESC的PRP凝胶进行根修复。DRZ一星期后，通过免疫荧光处理脊髓，以评估神经胶质反应（GFAP和Iba-1）和兴奋性突触回路（VGLUT1）的变化。术后八周，对腰部肿胀进行处理，以通过透射电子显微镜分析修复的微环境。通过电子冯·弗雷（Von Frey）方法评估脊柱反射恢复八周。诱导的hESCs中人FGF2的转录水平比未诱导的和野生型对应物高37倍以上。总之，结果表明，hESCs与PRP凝胶的结合促进了DRZ后实质性和突出的轴突再生过程。因此，如果适当地进行了背根的修复，则可以认为是在背根切开术后恢复感觉运动功能的一种方法。