Periostin enhances adipose-derived stem cell adhesion, migration, and therapeutic efficiency in Apo E deficient mice with hind limb ischemia.
Periostin enhances adipose-derived stem cell adhesion, migration, and therapeutic efficiency in Apo E deficient mice with hind limb ischemia.
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Periostin 增强 Apo E 缺陷小鼠后肢缺血的脂肪干细胞粘附、迁移和治疗效率
DOI：
10.1186/s13287-015-0126-x
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发表时间：
2015-07-24
影响因子：
7.5
通讯作者：
Lu X
中科院分区：
文献类型：
--
作者：
Qin J;Yuan F;Peng Z;Ye K;Yang X;Huang L;Jiang M;Lu X
前言移植自体/异基因脂肪干细胞(ADSCs)治疗血管生成是治疗严重缺血性疾病的潜在途径。然而，细胞移植到靶区后，细胞的存活、黏附、迁移和分化能力较差，限制了治疗效果。Periostin是一种细胞外基质蛋白，在创伤修复、促进细胞黏附、存活和血管生成等方面发挥重要作用。分析P-ADSCs在低氧条件下的存活、增殖、迁移和凋亡情况。此外，将P-ADSCs移植到载脂蛋白E缺陷的后肢缺血小鼠体内。检测激光多普勒血流灌注指数、免疫荧光和组织病理学检查，评价治疗效果。结果体外实验表明，Periostin基因修饰的ADSCs(P-ADSCs)可促进ADSCs的存活、增殖和迁移。在低氧条件下，ADSCs的凋亡受到抑制。术后4周，P-ADSCs组激光多普勒血流灌注指数明显高于ADSC组和对照组。免疫荧光和组织病理学检测显示，P-ADSCs位于缺血区及其周围，部分细胞分化为毛细血管和内皮细胞。P-ADSCs组的微血管密度明显高于对照组。Periostin的作用机制可能与上调整合素β1/FAK/PI3K/Akt/eNOS信号通路和促进生长因子的分泌有关。结论通过基因转导Periostin促进ADSCs的存活、迁移和疗效，将为重症肢体缺血的治疗提供新的思路。
IntroductionTherapeutic angiogenesis by transplantation of autologous/allogeneic adipose-derived stem cells (ADSCs) is a potential approach for severe ischemic diseases. However, poor viability, adhesion, migration and differentiation limit the therapeutic efficiency after the cells were transplanted into the targeted area. Periostin, an extracellular matrix protein, exhibits a critical role in wound repair as well as promotes cell adhesion, survival, and angiogenesis.MethodADSCs were obtained and genetically engineered with periostin gene (P-ADSCs). The viability, proliferation, migration, and apoptosis of P-ADSCs under hypoxia were analyzed. Moreover, P-ADSCs were implanted into Apo E deficient mice with hind limb ischemia. The Laser Doppler perfusion index, immunofluorescence, and histological pathology assay were tested to evaluate the therapeutic effects. The associated molecular mechanism of periostin on the proliferation, adhesion, migration, and differentiation of ADSCs was also analyzed.ResultsThe in vitro studies have shown that periostin-transfected ADSCs (P-ADSCs) promoted viability, proliferation, and migration of ADSCs. Apoptosis of ADSCs was inhibited under hypoxic conditions. The Laser Doppler perfusion index was significantly higher in the P-ADSCs group compared with that in the ADSC and control groups after 4 weeks. Immunofluorescence and histological pathology assay showed that the P-ADSCs were in and around the ischemic sites, and some cells differentiated into capillaries and endothelium. Microvessel densities were significantly improved in P-ADSCs group compared with those in the control group. The molecular mechanisms that provide the beneficial effects of periostin were connected with the upregulated expression of integrinβ1/FAK/PI3K/Akt/eNOS signal pathway and the increased secretion of growth factors.ConclusionOverexpression of periostin by gene transfection on ADSCs promotes survival, migration, and therapeutic efficiency, which will bring new insights into the treatment of critical limb ischemia.