Local delivery of FK506 to a nerve allograft is comparable to systemic delivery at suppressing allogeneic graft rejection.
Local delivery of FK506 to a nerve allograft is comparable to systemic delivery at suppressing allogeneic graft rejection.
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DOI：
10.1371/journal.pone.0281911
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
这项研究的目的是确定局部注射FK506是否能够阻止同种异体神经移植排斥反应足够长的时间，使轴突再生通过神经移植。用同种异体神经移植修复8 mm小鼠坐骨神经缺损处，观察局部FK506免疫抑制治疗的效果。使用负载FK506的聚(丙交酯-己内酯)神经导管将FK506持续局部输送到同种异体神经移植物。对照组采用FK506持续、暂时全身治疗同种异体神经移植和自体神经移植修复。对神经移植物组织中的炎性细胞和CD4+细胞的渗透进行了一系列评估，以表征随着时间的推移的免疫反应。神经再生和功能恢复通过神经组织形态计量学、腓肠肌质量恢复和梯级熟练运动试验进行系列评估。在研究结束时，第16周，所有的组都有相似程度的炎细胞渗透。局部FK506组和持续全身FK506组的CD4+细胞浸润水平相似，但显著高于自体移植对照组。在神经组织形态计量学方面，局部FK506组和连续系统FK506组的有髓轴突数量相似，但显著低于自体移植组和临时系统FK506组。自体移植组的肌肉质量恢复明显高于所有其他组。在梯级试验中，自体移植组、局部FK506组和持续全身FK506组的熟练运动能力水平相似，而临时全身FK506组的熟练运动能力明显好于所有其他组。这项研究的结果表明，局部注射FK506可以提供与全身注射FK506类似的免疫抑制和神经再生结果。
The objective of this study was to determine if locally delivered FK506 could prevent allogeneic nerve graft rejection long enough to allow axon regeneration to pass through the nerve graft. An 8mm mouse sciatic nerve gap injury repaired with a nerve allograft was used to assess the effectiveness of local FK506 immunosuppressive therapy. FK506-loaded poly(lactide-co-caprolactone) nerve conduits were used to provide sustained local FK506 delivery to nerve allografts. Continuous and temporary systemic FK506 therapy to nerve allografts, and autograft repair were used as control groups. Serial assessment of inflammatory cell and CD4+ cell infiltration into the nerve graft tissue was performed to characterize the immune response over time. Nerve regeneration and functional recovery was serially assessed by nerve histomorphometry, gastrocnemius muscle mass recovery, and the ladder rung skilled locomotion assay. At the end of the study, week 16, all the groups had similar levels of inflammatory cell infiltration. The local FK506 and continuous systemic FK506 groups had similar levels of CD4+ cell infiltration, however, it was significantly greater than the autograft control. In terms of nerve histmorphometry, the local FK506 and continunous systemic FK506 groups had similar amounts of myelinated axons, although they were significantly lower than the autograft and temporary systemic FK506 group. The autograft had significantly greater muscle mass recovery than all the other groups. In the ladder rung assay, the autograft, local FK506, and continuous systemic FK506 had similar levels of skilled locomotion performance, whereas the temporary systemic FK506 group had significanty better performance than all the other groups. The results of this study suggest that local delivery of FK506 can provide comparable immunosuppression and nerve regeneration outcomes as systemically delivered FK506.
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影响因子：
3.7
作者：
Bergler T;Jung B;Bourier F;Kühne L;Banas MC;Rümmele P;Wurm S;Banas B
通讯作者：
Banas B
影响因子：
6.1
作者：
Davis B;Wojtalewicz S;Labroo P;Shea J;Sant H;Gale B;Agarwal J
通讯作者：
Agarwal J
影响因子：
3.4
作者：
Davis, Brett;Hilgart, David;Agarwal, Jay
通讯作者：
Agarwal, Jay
影响因子：
4.1
作者：
Auba, Cristina;Hontanilla, Bernardo;Gorria, Oscar
通讯作者：
Gorria, Oscar
影响因子：
--
作者：
Grinsell D;Keating CP
通讯作者：
Keating CP