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接种于脱细胞神经同种异体移植物上的脂肪来源间充质干细胞可增强大鼠坐骨神经缺损模型中的血管生成。

Adipose derived mesenchymal stem cells seeded onto a decellularized nerve allograft enhances angiogenesis in a rat sciatic nerve defect model.

作者信息

Mathot Femke, Rbia Nadia, Bishop Allen T, Hovius Steven E R, Shin Alexander Y

机构信息

Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Department of Plastic Surgery, Radboudumc, Nijmegen, The Netherlands.

出版信息

Microsurgery. 2020 Jul;40(5):585-592. doi: 10.1002/micr.30579. Epub 2020 Mar 31.

Abstract

PURPOSE

Adipose derived mesenchymal stem cells (MSCs) are hypothesized to supplement tissues with growth factors essential for regeneration and neovascularization. The purpose of this study was to determine the effect of MSCs with respect to neoangiogenesis when seeded onto a decellularized nerve allograft in a rat sciatic nerve defect model.

METHODS

Allograft nerves were harvested from Sprague-Dawley rats and decellularized. MSCs were obtained from Lewis rats. 10 mm sciatic nerve defects in Lewis rats were reconstructed with reversed autograft nerves, decellularized allografts, decellularized allografts seeded with undifferentiated MSC or decellularized allografts seeded with differentiated MSCs. At 16 weeks, the vascular surface area and volume were evaluated.

RESULTS

The vascular surface area in normal nerves (34.9 ± 5.7%), autografts (29.5 ± 8.7%), allografts seeded with differentiated (38.9 ± 7.0%) and undifferentiated MSCs (29.2 ± 3.4%) did not significantly differ from each other. Unseeded allografts (21.2 ± 6.2%) had a significantly lower vascular surface area percentage than normal nonoperated nerves (13.7%, p = .001) and allografts seeded with differentiated MSCs (17.8%, p = .001). Although the vascular surface area was significantly correlated to the vascular volume (r = .416; p = .008), no significant differences were found between groups concerning vascular volumes. The vascularization pattern in allografts seeded with MSCs consisted of an extensive nonaligned network of microvessels with a centripetal pattern, while the vessels in autografts and normal nerves were more longitudinally aligned with longitudinal inosculation patterns.

CONCLUSIONS

Neoangiogenesis of decellularized allograft nerves was enhanced by stem cell seeding, in particular by differentiated MSCs. The pattern of vascularization was different between decellularized allograft nerves seeded with MSCs compared to autograft nerves.

摘要

目的

脂肪来源的间充质干细胞(MSCs)被认为可为组织补充再生和新血管形成所必需的生长因子。本研究的目的是在大鼠坐骨神经缺损模型中,确定将MSCs接种到脱细胞神经同种异体移植物上时对新生血管形成的影响。

方法

从Sprague-Dawley大鼠获取同种异体神经并进行脱细胞处理。MSCs取自Lewis大鼠。用逆行自体神经、脱细胞同种异体移植物、接种未分化MSCs的脱细胞同种异体移植物或接种分化MSCs的脱细胞同种异体移植物重建Lewis大鼠10毫米的坐骨神经缺损。在16周时,评估血管表面积和体积。

结果

正常神经(34.9±5.7%)、自体移植物(29.5±8.7%)、接种分化MSCs(38.9±7.0%)和未分化MSCs(29.2±3.4%)的同种异体移植物的血管表面积彼此之间无显著差异。未接种的同种异体移植物(21.2±6.2%)的血管表面积百分比显著低于正常未手术神经(13.7%,p = 0.001)和接种分化MSCs的同种异体移植物(17.8%,p = 0.001)。尽管血管表面积与血管体积显著相关(r = 0.416;p = 0.008),但各实验组之间的血管体积无显著差异。接种MSCs的同种异体移植物中的血管化模式由广泛的、排列不齐的微血管网络组成,呈向心模式,而自体移植物和正常神经中的血管则更多地纵向排列,呈纵向吻合模式。

结论

干细胞接种,特别是分化的MSCs,可增强脱细胞同种异体移植神经的新生血管形成。与自体移植神经相比,接种MSCs的脱细胞同种异体移植神经的血管化模式有所不同。

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