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A Strategy Toward Bridging a Complete Spinal Cord Lesion Using Stretch-Grown Axons.
Tissue Engineering, Part A ( IF 4.1 ) Pub Date : 2020-06-16 , DOI: 10.1089/ten.tea.2019.0230
Mindy Ezra Sadik 1 , Ali K Ozturk 2 , Ahmed Albayar 1 , Marc Branche 1 , Patricia Zadnik Sullivan 2 , Laura O Schlosser 1 , Kevin D Browne 1 , Andrew H Jaye 1 , Douglas H Smith 1
Affiliation  

In this study, we evaluated the ability of stretch-grown tissue-engineered nerve grafts (TENGs) to perform as a living scaffold for axonal regeneration across a severed spinal cord lesion. TENGs, consisting of stretch-grown axons spanning two populations of dorsal root ganglia neurons, have proven to be effective in bridging gaps in peripheral nerve injury. A complete transection was performed at the thoracic level in a rodent model and 5 mm of cord was completely removed. TENGs encapsulated in a collagen hydrogel were placed within the cavity and compared against a collagen only transplant. Through hematoxylin and eosin (H&E) staining and immunohistochemistry, we found that TENGs survived up to 6 weeks post-transplant, extending neuronal processes into and through host tissue early on in both the rostral and caudal direction. In several cases, TENG axons penetrated into and through glial scar tissue, appearing to overcome a common obstacle for axonal regeneration in spinal cord injuries (SCIs). H&E staining also provided evidence that animals treated with TENGs resulted in lesion sites with greater tissue infiltration and less compression than animals treated with a collagen hydrogel only, an encouraging finding given the severity of the injury model. We also observed effects the TENGs had on glial scar formation, cyst formation, and immune response at multiple time points as these are common difficulties faced in tissue engineering methods to treat or repair SCI. If able to address these universal challenges associated with SCI, TENGs may offer an alternative option in neural transplantation and may represent a viable tool in the multifaceted treatment of SCI.

中文翻译:

一种使用拉伸生长的轴突桥接完整脊髓病变的策略。

在这项研究中,我们评估了拉伸生长的组织工程神经移植物(TENGs)的功能,以作为整个脊髓损伤后轴突再生的活体支架。TENGs由跨越两个背根神经节神经元群体的伸展生长的轴突组成,已被证明可有效弥合周围神经损伤的间隙。在啮齿动物模型中,在胸腔水平进行完整的横切,并完全去除5毫米的脐带。将包封在胶原蛋白水凝胶中的TENG放置在腔内,并与仅胶原蛋白的移植物进行比较。通过苏木精和曙红(H&E)染色和免疫组织化学,我们发现TENGs在移植后存活了长达6周,使神经元突触在鼻端和尾端方向早期进入并通过宿主组织。在某些情况下,TENG轴突穿透并穿过神经胶质瘢痕组织,似乎克服了脊髓损伤(SCI)中轴突再生的常见障碍。H&E染色还提供了证据,与仅用胶原蛋白水凝胶治疗的动物相比,用TENGs治疗的动物导致的病变部位具有更大的组织浸润和更少的压迫感,这是一个令人鼓舞的发现,考虑到损伤模型的严重性。我们还观察到了TENGs在多个时间点对神经胶质瘢痕形成,囊肿形成和免疫反应的影响,因为这些是组织工程学方法治疗或修复SCI面临的常见困难。如果能够解决与SCI相关的这些普遍挑战,则TENG可能会在神经移植中提供另一种选择,并且可能是SCI多方面治疗中的可行工具。
更新日期:2020-06-18
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