Vascularized adipose tissue grafts from human mesenchymal stem cells with bioactive cues and microchannel conduits.

Michael S Stosich, Barb Bastian, Nicholas W Marion, Paul A Clark, Gwendolen Reilly, Jeremy J Mao
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Abstract

Vascularization is critical to the survival of engineered tissues. This study combined biophysical and bioactive approaches to induce neovascularization in vivo. Further, we tested the effects of engineered vascularization on adipose tissue grafts. Hydrogel cylinders were fabricated from poly(ethylene glycol) diacrylate (PEG) in four configurations: PEG alone, PEG with basic fibroblast growth factor (bFGF), microchanneled PEG, or both bFGF-adsorbed and microchanneled PEG. In vivo implantation revealed no neovascularization in PEG, but substantial angiogenesis in bFGF-adsorbed and/or microchanneled PEG. The infiltrating host tissue consisted of erythrocyte-filled blood vessels lined by endothelial cells, and immunolocalized to vascular endothelial growth factor (VEGF). Human mesenchymal stem cells were differentiated into adipogenic cells, and encapsulated in PEG with both microchanneled and adsorbed bFGF. Upon in vivo implantation subcutaneously in immunodeficient mice, oil red O positive adipose tissue was present and interspersed with interstitial fibrous (IF) capsules. VEGF was immunolocalized in the IF capsules surrounding the engineered adipose tissue. These findings suggest that bioactive cues and/or microchannels promote the genesis of vascularized tissue phenotypes such as the tested adipose tissue grafts. Especially, engineered microchannels may provide a generic approach for modifying existing biomaterials by providing conduits for vascularization and/or diffusion.

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利用生物活性线索和微通道导管从人类间充质干细胞中提取血管化脂肪组织移植物。
血管化对工程组织的存活至关重要。本研究结合生物物理和生物活性方法诱导体内新生血管。此外,我们还测试了工程血管化对脂肪组织移植物的影响。水凝胶圆柱体由聚(乙二醇)二丙烯酸酯(PEG)以四种配置制成:这四种结构分别是:单独的 PEG、含有碱性成纤维细胞生长因子(bFGF)的 PEG、微通道 PEG 或同时吸附了 bFGF 和微通道 PEG 的 PEG。体内植入后发现,PEG 没有新生血管,但吸附了碱性成纤维细胞生长因子和/或微通道的 PEG 有大量血管生成。浸润的宿主组织由内皮细胞衬里的充满红细胞的血管组成,并对血管内皮生长因子(VEGF)进行免疫定位。人类间充质干细胞被分化成脂肪形成细胞,并包裹在含有微通道和吸附 bFGF 的 PEG 中。体内植入免疫缺陷小鼠皮下后,出现了油红 O 阳性脂肪组织,并与间质纤维(IF)囊相间。血管内皮生长因子免疫定位在工程脂肪组织周围的 IF 胶囊中。这些发现表明,生物活性线索和/或微通道可促进血管化组织表型的形成,如测试的脂肪组织移植物。特别是,工程微通道可为血管化和/或扩散提供通道,从而为改造现有生物材料提供通用方法。
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Tissue engineering
Tissue engineering CELL & TISSUE ENGINEERING-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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Cartilage reshaping via in vitro mechanical loading. ECM molecules mediate both Schwann cell proliferation and activation to enhance neurite outgrowth. Development of custom-built bone scaffolds using mesenchymal stem cells and apatite-wollastonite glass-ceramics. Vascularized adipose tissue grafts from human mesenchymal stem cells with bioactive cues and microchannel conduits. A novel time-varying poly lactic-co glycolic acid external sheath for vein grafts designed under physiological loading.
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