Hoben Gwendolyn M, Ee Xueping, Schellhardt Lauren, Yan Ying, Hunter Daniel A, Moore Amy M, Snyder-Warwick Alison K, Stewart Sheila, Mackinnon Susan E, Wood Matthew D
From the Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine; and the Division of Cell Biology and Physiology, Washington University.
Plast Reconstr Surg. 2018 Oct;142(4):952-961. doi: 10.1097/PRS.0000000000004759.
Nerve grafting with an autograft is considered the gold standard. However, the functional outcomes of long (>3 cm) nerve autografting are often poor. The authors hypothesized that a factor contributing to these outcomes is the graft microenvironment, where long compared to short autografts support axon regeneration to different extents.
A rat sciatic nerve defect model was used to compare regeneration in short (2 cm) and long (6 cm) isografts. Axon regeneration and cell populations within grafts were assessed using histology, retrograde labeling of neurons regenerating axons, immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction, and electron microscopy at 4 and/or 8 weeks.
At 8 weeks, for distances of both 1 and 2 cm from the proximal coaptation (equivalent regenerative distance), long isografts had reduced numbers of regenerated fibers compared with short isografts. Similarly, the number of motoneurons regenerating axons was reduced in the presence of long isografts compared with short isografts. Considering the regenerative microenvironments between short and long isografts, cell densities and general populations within both short and long isografts were similar. However, long isografts had significantly greater expression of senescence markers, which included senescence-associated β-galactosidase, p21, and p16, and distinct chromatin changes within Schwann cells.
This study shows that axon regeneration is reduced in long compared with short isografts, where long isografts contained an environment with an increased accumulation of senescent markers. Although autografts are considered the gold standard for grafting, these results demonstrate that we must continue to strive for improvements in the autograft regenerative environment.
自体神经移植被认为是金标准。然而，长距离（>3厘米）自体神经移植的功能结果往往不佳。作者推测导致这些结果的一个因素是移植微环境，与短自体移植相比，长自体移植在不同程度上支持轴突再生。
使用大鼠坐骨神经缺损模型比较短（2厘米）和长（6厘米）同基因移植中的再生情况。在4周和/或8周时，使用组织学、再生轴突的神经元逆行标记、免疫组织化学、定量逆转录聚合酶链反应和电子显微镜评估移植内的轴突再生和细胞群体。
在8周时，对于距近端吻合处1厘米和2厘米的距离（等效再生距离），与短同基因移植相比，长同基因移植的再生纤维数量减少。同样，与短同基因移植相比，在存在长同基因移植的情况下，再生轴突的运动神经元数量减少。考虑到短和长同基因移植之间的再生微环境，短和长同基因移植内的细胞密度和总体细胞群体相似。然而，长同基因移植中衰老标志物的表达明显更高，其中包括衰老相关β-半乳糖苷酶、p21和p16，并且雪旺细胞内有明显的染色质变化。
本研究表明，与短同基因移植相比，长同基因移植中的轴突再生减少，长同基因移植包含一个衰老标志物积累增加的环境。尽管自体移植被认为是移植的金标准，但这些结果表明我们必须继续努力改善自体移植的再生环境。
