Keating Timothy, Isaacs Jonathan, Mallu Satya, Baxi Mihir
Division of Hand Surgery, Department of Orthopaedic Surgery, Virginia Commonwealth University Medical Center, Richmond, VA, USA.
Division of Hand Surgery, Department of Orthopaedic Surgery, Virginia Commonwealth University Medical Center, Richmond, VA, USA.
J Neurosci Methods. 2015 Jul 15;249:92-8. doi: 10.1016/j.jneumeth.2015.04.012. Epub 2015 Apr 30.
Although human acellular nerve allograft is a promising nerve repair tool, optimizing graft application and understanding effective graft dimensions has been hampered by lack of an appropriate animal model. Rodent nerve acellular allograft can be tested in the utilitarian rodent nerve repair model, but testing different size options is limited by the size of the rodent donor animal. Human acellular nerve allograft offers the variety of sizes desired for more complete study but poses a high risk of rejection as xenograft tissue in the rodent model. Athymic nude rats are less prone to reject xenograft tissue due to their immunocompromised state and may offer an animal model for testing human acellular allograft.
Fifteen athymic nude and 15 Sprague-Dawley rats underwent unilateral excision and repair of a 10mm tibial nerve segment using 10mm of human acellular nerve graft. Testing at 3 months consisted of muscle force measurements, wet muscle weight, and histological assessment from the middle of the nerve grafts.
Athymic rats repaired with human acellular xenograft demonstrated higher reinnervated muscle weight Gross inspection of the xenograft in euthymic rats revealed a brown and scarred center and histological inspection demonstrated larger axon diameters, and higher midgraft axon counts in the grafts of athymic rats.
The athymic rat has been used in many studies that require an immunocompromised host, including implantation of foreign nervous tissue. Previous attempts at implanting acellular nerve xenograft into immunocompetent rats have yielded suboptimal results when compared to allograft. This study is the first to test acellular human nerve allograft in an athymic rat.
The nerve regeneration was better in human acellular nerve allograft implanted into immunocompromised athymic rats when compared to euthymic rats supporting a potential role of this model in studying acellular human nerve tissue.
尽管人脱细胞神经同种异体移植物是一种很有前景的神经修复工具,但由于缺乏合适的动物模型,优化移植物应用和了解有效的移植物尺寸受到了阻碍。啮齿动物神经脱细胞同种异体移植物可在实用的啮齿动物神经修复模型中进行测试,但测试不同尺寸选项受到啮齿动物供体动物大小的限制。人脱细胞神经同种异体移植物提供了更全面研究所需的各种尺寸,但在啮齿动物模型中作为异种移植组织存在较高的排斥风险。无胸腺裸鼠由于其免疫受损状态,较不易排斥异种移植组织,可能为测试人脱细胞同种异体移植物提供一种动物模型。
15只无胸腺裸鼠和15只Sprague-Dawley大鼠使用10mm的人脱细胞神经移植物对10mm的胫神经节段进行单侧切除和修复。3个月时的测试包括肌肉力量测量、湿肌肉重量以及神经移植物中部的组织学评估。
用人脱细胞异种移植物修复的无胸腺大鼠显示出更高的再支配肌肉重量。对有胸腺大鼠的异种移植物进行大体检查发现中心呈褐色且有瘢痕,组织学检查显示无胸腺大鼠移植物中的轴突直径更大,移植物中部的轴突计数更高。
无胸腺大鼠已用于许多需要免疫受损宿主的研究,包括植入外来神经组织。与同种异体移植相比,先前将脱细胞神经异种移植物植入有免疫能力大鼠的尝试效果欠佳。本研究是首次在无胸腺大鼠中测试脱细胞人神经同种异体移植物。
与人有胸腺大鼠相比,将人脱细胞神经同种异体移植物植入免疫受损的无胸腺大鼠时神经再生更好,这支持了该模型在研究脱细胞人神经组织方面的潜在作用。