Improvement of the Survival of Human Autologous Fat Transplantation by Using VEGF-Transfected Adipose-Derived Stem Cells
Improvement of the Survival of Human Autologous Fat Transplantation by Using VEGF-Transfected Adipose-Derived Stem Cells
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使用转染 VEGF 的脂肪干细胞提高人类自体脂肪移植的存活率
DOI：
10.1097/prs.0b013e3181babbb6
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发表时间：
2009-11-01
影响因子：
3.6
通讯作者：
Fu, Bingchuan
中科院分区：
文献类型：
--
作者：
Lu, Feng;Li, Jie;Fu, Bingchuan
背景：自体脂肪移植的疗效因脂肪吸收和脂肪坏死引起的纤维化而降低。移植后早期增强移植新生血管可能会减少这些结果。作者询问使用血管内皮生长因子（VEGF）转导的脂肪源性干细胞进行细胞和伴随基因治疗是否能改善脂肪移植的新生血管和存活。方法：人脂肪源性干细胞体外扩增三代，用1,1 ' -二十八烷基-3,3,3 ',3 ' -四甲基吲哚碳菁（DiI）标记，用VEGF转导或不转导。然后将人体脂肪组织与dii标记的vegf转导的脂肪来源干细胞、dii标记的脂肪来源干细胞、已知的血管生成促进剂胰岛素或单独的培养基混合，然后将18只裸鼠皮下注射这四种制剂，在四个指定的位置随机接受这四种混合物中的一种。6个月后，评估移植组织的体积和组织学，并通过计数毛细血管来量化新生血管的形成。结果：对照移植存活率为27.1%±8.2%，但与vegf转导和vegf未转导的干细胞混合可显著提高移植存活率（分别为74.1±12.6%和60.1±17.6%）。胰岛素效果较差（37.7%±6.9%）。组织学分析显示，与对照移植不同，两种类型的移植主要由脂肪组织组成，并且脂肪坏死和纤维化明显减少。vegf转导的脂肪源性干细胞处理的移植具有明显高于其他移植的毛细血管密度，并且具有dii双阳性和cd31双阳性细胞（即脂肪源性干细胞衍生的内皮细胞）。结论：脂肪源性干细胞联合VEGF转导可提高移植脂肪组织的存活率和质量。
Background: The efficacy of autologous fat transplantation is reduced by fat absorption and fibrosis due to fat necrosis. Enhanced transplant neovascularization early after transplantation may reduce these outcomes. The authors asked whether cell and concomitant gene therapy using adipose-derived stem cells transduced with vascular endothelial growth factor (VEGF) improves fat transplant neovascularization and survival. Methods: Human adipose-derived stem cells were expanded ex vivo for three passages, labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine (DiI), and transduced with VEGF or left untransduced. Human fat tissues were then mixed with the DiI-labeled VEGF-transduced adipose-derived stem cells, the DiI-labeled adipose-derived stem cells, the known vascularization-promoting agent insulin, or medium alone, and 18 nude mice were injected subcutaneously with all four preparations, with each of the four designated spots receiving one of these four mixtures in a random fashion. Six months later, transplanted tissue volume and histology were evaluated and neovascularization was quantified by counting the capillaries. Results: Control transplant survival was 27.1 ± 8.2 percent, but mixture with the VEGF-transduced and VEGF-untransduced stem cells significantly increased transplant survival (74.1 ± 12.6 percent and 60.1 ± 17.6 percent, respectively). Insulin was less effective (37.7 ± 6.9 percent). Histological analysis revealed both types of transplants consisted predominantly of adipose tissue, unlike the control transplants, and had significantly less fat necrosis and fibrosis. The VEGF-transduced, adipose-derived stem cell–treated transplants had significantly higher capillary density than the other transplants and bore DiI-double-positive and CD31-double-positive cells (i.e., adipose-derived stem cell–derived endothelial cells). Conclusion: Adipose-derived stem cells together with VEGF transduction can enhance the survival and quality of transplanted fat tissues.