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基质血管成分细胞加持续释放 VEGF/Ang-1-PLGA 微球可提高小鼠脂肪移植物的存活率。

Stromal vascular fraction cells plus sustained release VEGF/Ang-1-PLGA microspheres improve fat graft survival in mice.

机构信息

First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

J Cell Physiol. 2019 May;234(5):6136-6146. doi: 10.1002/jcp.27368. Epub 2018 Sep 21.

Abstract

Autologous fat transplantation is increasingly applied in plastic and reconstructive surgery. Stromal vascular fraction cells (SVFs) combined with angiogenic factors, such as VEGF (vascular endothelial growth factor A) and Ang-1 (angiogenin-1), can improve angiogenesis, which is a critical factor for graft survival. However, direct transplant with such a mixture is insufficient owing to the short half-life of angiogenic factors. In this study, we evaluated whether a double sustained release system of VEGF/ANG-1-PLGA (poly (lactic-co-glycolic acid)) microspheres plus SVFs can improve angiogenesis and graft survival after autologous fat transplantation. VEGF/ANG-1-PLGA-sustained release microspheres were fabricated by a modified double emulsion-solvent evaporation technique. Human aspirated fat was mixed with SVF suspension plus VEGF/ANG-1 sustained release microspheres (Group C), SVF suspension (Group B) alone, or Dulbecco's modified Eagle's medium as the control (Group A). Eighteen immunocompromised nude mice were injected with these three mixtures subcutaneously at random positions. After 8 weeks, the mean volume of grafts was greater in the SVFs plus VEGF/ANG-1-PLGA group than in the control and SVFs groups (1.08 ± 0.069 ml vs. 0.62 ± 0.036 ml, and 0.83 ± 0.059 ml, respectively). Histological assessments showed that lower fibrosis, but greater microvascular density in the SVFs plus VEGF/ANG-1-PLGA group than in the other groups, though the SVFs group also had an appropriate capillary density and reduced fibrosis. Our findings indicate that SVFs plus VEGF/ANG-1-PLGA-sustained release microspheres can improve angiogenesis and graft survival after autologous fat transplantation.

摘要

自体脂肪移植在整形和重建外科中应用日益广泛。基质血管成分细胞(SVFs)与血管生成因子(如 VEGF(血管内皮生长因子 A)和 Ang-1(血管生成素-1))结合可促进血管生成,这是移植物存活的关键因素。然而,由于血管生成因子的半衰期短,直接移植这种混合物是不够的。在这项研究中,我们评估了 VEGF/ANG-1-PLGA(聚(乳酸-共-乙醇酸))微球加 SVFs 的双持续释放系统是否可以改善自体脂肪移植后的血管生成和移植物存活。通过改良的双乳液-溶剂蒸发技术制备 VEGF/ANG-1-PLGA 持续释放微球。将人抽吸脂肪与 SVF 悬浮液加 VEGF/ANG-1 持续释放微球(C 组)、SVF 悬浮液(B 组)或杜氏改良伊格尔培养基(A 组)混合。将这三种混合物随机注射到 18 只免疫缺陷裸鼠的皮下。8 周后,SVFs 加 VEGF/ANG-1-PLGA 组的移植物平均体积大于对照组和 SVFs 组(1.08±0.069ml 比 0.62±0.036ml 和 0.83±0.059ml)。组织学评估显示,SVFs 加 VEGF/ANG-1-PLGA 组的纤维化程度较低,但微血管密度较高,而其他两组的毛细血管密度也适当,纤维化程度降低。我们的研究结果表明,SVFs 加 VEGF/ANG-1-PLGA 持续释放微球可以改善自体脂肪移植后的血管生成和移植物存活。

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