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Abstract：
BACKGROUND: A detailed three-dimensional (3D) evaluation of microvasculature is evolving to be a powerful tool, providing mechanistic understanding of angiomodulating strategies. The aim of this study was to evaluate the microvascular architecture of nerve allografts after combined stem cell delivery and surgical angiogenesis in a rat sciatic nerve defect model.
METHODS: In 25 Lewis rats, sciatic nerve gaps were repaired with (i) autografts, (ii) allografts, (iii) allografts wrapped in a pedicled superficial inferior epigastric artery fascia (SIEF) flap to provide surgical angiogenesis, combined with (iv) undifferentiated mesenchymal stem cells (MSC) and (v) MSCs differentiated into Schwann cell-like cells. At two weeks, vascular volume was measured using microcomputed tomography, and percentage and volume of vessels at different diameters were evaluated and compared with controls.
RESULTS: The vascular volume was significantly greatest in allografts treated with undifferentiated MSCs and surgical angiogenesis combined as compared to all experimental groups (P<0.01 as compared to autografts, P<0.0001 to allografts, and P<0.05 to SIEF and SIEF combined with differentiated MSCs, respectively). Volume and diameters of vessel segments in nerve allografts were enhanced by surgical angiogenesis. These distributions were further improved when surgical angiogenesis was combined with stem cells, with greatest increase found when combined with undifferentiated MSCs.
CONCLUSIONS: The interaction between vascularity and stem cells remains complex, however, this study provides some insight into its synergistic mechanisms. The combination of surgical angiogenesis with undifferentiated MSCs specifically, results in the greatest increase in revascularization, size of vessels, and stimulation of vessels to reach the middle longitudinal third of the nerve allograft.
METHODS: In 25 Lewis rats, sciatic nerve gaps were repaired with (i) autografts, (ii) allografts, (iii) allografts wrapped in a pedicled superficial inferior epigastric artery fascia (SIEF) flap to provide surgical angiogenesis, combined with (iv) undifferentiated mesenchymal stem cells (MSC) and (v) MSCs differentiated into Schwann cell-like cells. At two weeks, vascular volume was measured using microcomputed tomography, and percentage and volume of vessels at different diameters were evaluated and compared with controls.
RESULTS: The vascular volume was significantly greatest in allografts treated with undifferentiated MSCs and surgical angiogenesis combined as compared to all experimental groups (P<0.01 as compared to autografts, P<0.0001 to allografts, and P<0.05 to SIEF and SIEF combined with differentiated MSCs, respectively). Volume and diameters of vessel segments in nerve allografts were enhanced by surgical angiogenesis. These distributions were further improved when surgical angiogenesis was combined with stem cells, with greatest increase found when combined with undifferentiated MSCs.
CONCLUSIONS: The interaction between vascularity and stem cells remains complex, however, this study provides some insight into its synergistic mechanisms. The combination of surgical angiogenesis with undifferentiated MSCs specifically, results in the greatest increase in revascularization, size of vessels, and stimulation of vessels to reach the middle longitudinal third of the nerve allograft.
摘要：
背景：对微脉管系统进行详细的三维（3D）评估正在发展成为一种强大的工具，提供对血管调制策略的机械理解。这项研究的目的是评估大鼠坐骨神经缺损模型中干细胞递送和手术血管生成相结合后神经同种异体移植物的微血管结构。
方法：在25只Lewis大鼠中，坐骨神经间隙用（i）自体移植物修复，(ii)同种异体移植物，（iii）同种异体移植物包裹在带蒂的上腹部下动脉筋膜（SIEF）皮瓣中，以提供外科血管生成，与（iv）未分化的间充质干细胞（MSC）和（v）分化为雪旺样细胞的MSC组合。两周后，使用显微计算机断层扫描测量血管体积，评估不同直径血管的百分比和体积，并与对照组进行比较。
结果：与所有实验组相比，未分化MSCs和手术血管生成联合治疗的同种异体移植物的血管体积显着最大（与自体移植物相比，P<0.01，同种异体移植物P<0.0001，SIEF和SIEF联合分化MSCs,P<0.05,分别)。手术血管生成增加了同种异体神经移植物中血管段的体积和直径。当手术血管生成与干细胞结合时，这些分布进一步改善，当与未分化的MSC结合时发现最大的增加。
结论：血管和干细胞之间的相互作用仍然很复杂，然而,这项研究提供了对其协同机制的一些见解。手术血管生成与未分化的MSCs特异性结合,导致血运重建的最大增加，血管的大小，并刺激血管到达同种异体神经移植物的中间纵向三分之一。
方法：在25只Lewis大鼠中，坐骨神经间隙用（i）自体移植物修复，(ii)同种异体移植物，（iii）同种异体移植物包裹在带蒂的上腹部下动脉筋膜（SIEF）皮瓣中，以提供外科血管生成，与（iv）未分化的间充质干细胞（MSC）和（v）分化为雪旺样细胞的MSC组合。两周后，使用显微计算机断层扫描测量血管体积，评估不同直径血管的百分比和体积，并与对照组进行比较。
结果：与所有实验组相比，未分化MSCs和手术血管生成联合治疗的同种异体移植物的血管体积显着最大（与自体移植物相比，P<0.01，同种异体移植物P<0.0001，SIEF和SIEF联合分化MSCs,P<0.05,分别)。手术血管生成增加了同种异体神经移植物中血管段的体积和直径。当手术血管生成与干细胞结合时，这些分布进一步改善，当与未分化的MSC结合时发现最大的增加。
结论：血管和干细胞之间的相互作用仍然很复杂，然而,这项研究提供了对其协同机制的一些见解。手术血管生成与未分化的MSCs特异性结合,导致血运重建的最大增加，血管的大小，并刺激血管到达同种异体神经移植物的中间纵向三分之一。
