Use of cold-preserved allografts seeded with autologous Schwann cells in the treatment of a long-gap peripheral nerve injury

Use of cold-preserved allografts seeded with autologous Schwann cells in the treatment of a long-gap peripheral nerve injury
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DOI:
10.1097/01.prs.0000245341.71666.97
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发表时间:
2007-01-01
影响因子:
3.6
通讯作者:
Mackinnon, Susan E.
Mackinnon, Susan E.
中科院分区:
医学1区
文献类型:
--
作者:
Hess, Jason R.;Brenner, Michael J.;Mackinnon, Susan E.

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背景:自体组织的局限性激发了对修复复杂周围神经损伤的替代材料的研究。尸体同种异体移植物是一种潜在的重建材料,但它们的使用需要全身免疫抑制。冷保存(7周)使同种异体移植物缺乏抗原,但这些无细胞基质通常不能支持超过3 cm的再生。在这项研究中,作者评估了重建广泛的非人灵长类动物周围神经缺损使用7周的冷保存同种异体移植物再填充培养自体施万cells.Methods:10远交食蟹猴灵长类动物配对的基础上,最大的遗传差异,通过相似性指数测定。共14个尺神经缺损测量6厘米成功重建自体移植物(n = 5),新鲜同种异体移植物(n = 2),冷保存同种异体移植物(n = 3),或冷保存同种异体移植物接种自体雪旺细胞(n = 4)。通过酶联免疫吸附斑点试验,和神经收获在6个月的组织学和histomorphometric analysis.Results:细胞因子的生产在响应冷保存同种异体移植物和冷保存同种异体移植物接种自体雪旺细胞进行评估,观察到的自体移植物相似。雪旺细胞再填充冷保存移植物表现出显着增强的纤维计数,神经密度,和百分比的神经(p < 0.05)相比,unseeded冷保存的移植物在6个月后reconstruction.Conclusions:冷保存同种异体移植物接种自体雪旺细胞在无关的受体耐受性良好,并支持显着再生跨越6厘米周围神经缺损。使用冷保存的同种异体神经组织补充自体Schwarm细胞提出了一个潜在的安全和有效的替代使用自体组织在重建广泛的神经损伤。
Background: Limitations in autogenous tissue have inspired the study of alternative materials for repair of complex peripheral nerve injuries. Cadaveric allografts are one potential reconstructive material, but their use requires systemic immunosuppression. Cold preservation (7 weeks) renders allografts devoid of antigens, but these acellular substrates generally fail in supporting regeneration beyond 3 cm. In this study, the authors evaluated the reconstruction of extensive nonhuman primate peripheral nerve defects using 7-week cold-preserved allografts repopulated with cultured autologous Schwann cells.Methods: Ten outbred Macaca fascicularis primates were paired based on maximal genetic disparity as measured by similarity index assay. A total of 14 ulnar nerve defects measuring 6 cm were successfully reconstructed using autografts (n = 5), fresh allografts (n = 2), cold-preserved allografts (n = 3), or cold-preserved allografts seeded with autogenous Schwann cells (n 4). Recipient immunoreactivity was evaluated by means of enzyme-linked immunosorbent spot assay, and nerves were harvested at 6 months for histologic and histomorphometric analysis.Results: Cytokine production in response to cold-preserved allografts and cold-preserved allografts seeded with autologous Schwann cells was similar to that observed for autografts. Schwann cell-repopulated cold-preserved grafts demonstrated significantly enhanced fiber counts, nerve density, and percentage nerve (p < 0.05) compared with unseeded cold-preserved grafts at 6 months after reconstruction.Conclusions: Cold-preserved allografts seeded with autologous Schwann cells were well-tolerated in unrelated recipients and supported significant regeneration across 6-cm peripheral nerve defects. Use of cold-preserved allogeneic nerve tissue supplemented with autogenous Schwarm cells poses a potentially safe and effective alternative to the use of autologous tissue in the reconstruction of extensive nerve injuries.