Trambitas Cristian, Pap Timea, Niculescu Raluca, Popelea Maria Catalina, Cotoi Ovidiu S, Cordoș Bogdan, Domnariu Horatiu-Paul, Marin Andrei, Feier Andrei Marian, David Camelia, Vintila Cristian
Plastic and Reconstructive Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, ROU.
Pathology and Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, ROU.
Cureus. 2024 Jun 14;16(6):e62412. doi: 10.7759/cureus.62412. eCollection 2024 Jun.
Peripheral nerve injuries are a significant clinical challenge. The rat sciatic nerve serves as an ideal model for studying nerve regeneration. Extensive research has been conducted to unravel the intricate mechanisms involved in peripheral nerve regeneration, aiming to develop effective therapeutic strategies for nerve injury patients. Research including different types of materials that can be used as nerve guides like synthetic polymers have been investigated for their biocompatibility and molding properties. Among multiple stem cell types, adipose-derived stem cells (ASCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), and induced pluripotent stem cells (iPSCs) have shown neuroprotective and regenerative important properties.
The purposes of our study were to develop a protocol for rat sciatic nerve injury treated with 3D-printed guide and adipose stem cells to investigate nerve regeneration through histologic examination and biomechanical characteristics of muscular tissue. We use 20 (100%) male Wistar rats, measuring between 350 g ± 35 g, who underwent complete transection of the right sciatic nerve, resulting in a 1 cm defect. The group was separated into three subgroups: the first subgroup (n = 8) was treated with a 3D-printed guide with adipose stem cells, the second subgroup (n = 8) was treated with a 3D-printed guide without adipose stem cells, and the third subgroup (n = 4) was the control group. At four, eight, and 12 weeks, we measured with ultrasonography the grade of muscular atrophy. At 12 weeks, we harvested the sciatic nerve and performed a histological examination and mechanical investigation of the tibialis anterior muscle.
On the examined specimen of the first subgroup, cross-sectioned nerve structures were present, surrounded by a mature fibro-adipose connective tissue, with blood vessels. In the second subgroup, no nerve structure was observed on the examined sections, but in the polymorphic inflammatory infiltrate and control group, no signs of regeneration were found.
The present study shows a promising potential when utilizing adipose stem cell-based therapies for promoting peripheral nerve regeneration following large (>1 cm) nerve defects knowing that at this size, regeneration is impossible with known treatments.
周围神经损伤是一项重大的临床挑战。大鼠坐骨神经是研究神经再生的理想模型。人们已经进行了广泛的研究,以阐明周围神经再生所涉及的复杂机制,旨在为神经损伤患者开发有效的治疗策略。包括合成聚合物等可作为神经导管的不同类型材料在内的研究,已对其生物相容性和成型特性进行了调查。在多种干细胞类型中,脂肪来源干细胞(ASC)、骨髓来源间充质干细胞(BM-MSC)和诱导多能干细胞(iPSC)已显示出神经保护和再生的重要特性。
我们研究的目的是制定一种用3D打印导管和脂肪干细胞治疗大鼠坐骨神经损伤的方案,通过组织学检查和肌肉组织的生物力学特性来研究神经再生。我们使用20只(100%)体重在350 g±35 g之间的雄性Wistar大鼠,其右侧坐骨神经被完全横断,造成1 cm的缺损。该组被分为三个亚组:第一个亚组(n = 8)用含有脂肪干细胞的3D打印导管治疗,第二个亚组(n = 8)用不含脂肪干细胞的3D打印导管治疗,第三个亚组(n = 4)为对照组。在4周、8周和12周时,我们用超声测量肌肉萎缩程度。在12周时,我们采集坐骨神经并对胫前肌进行组织学检查和力学研究。
在第一个亚组的检查标本上,存在横切的神经结构,周围是成熟的纤维脂肪结缔组织,并伴有血管。在第二个亚组中,检查切片上未观察到神经结构,但在多形性炎症浸润和对照组中,未发现再生迹象。
本研究表明,在已知对于大于1 cm的神经缺损,现有治疗方法无法实现再生的情况下,利用基于脂肪干细胞的疗法促进周围神经再生具有很大的潜力。