Engineered Human Adipose-Derived Stem Cells Inducing Endothelial Lineage and Angiogenic Response

工程化人类脂肪干细胞诱导内皮细胞系和血管生成反应

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作者:Amita Ajit, T R Santhosh Kumar, Lissy K Krishnan

Abstract

With respect to the persistent hunt for a cytocompatible, translational, reproducible, and effective approach in engineering primary human adipose-derived mesenchymal stromal cells (hADMSCs), we demonstrate the application of Neon® Transfection System in adequate transient delivery of angiogenic factors. The study presents functional assessment of this approach in vitro, with two notable outcomes at translational perspective; (1) Bioengineered hADMSCs secretome does induce endothelial lineage commitment of stem cells at both transcriptional and translational levels and (2) Combinatorial delivery of vascular endothelial growth factor A and hypoxia-inducible factor-1α by bioengineered hADMSCs enhance upregulation of endothelial cell proliferation, migration-associated wound closure, and endothelial tube formation with augmented Flk-1 expression, as compared with their independent actions. The methods described in this study paves way for in vivo evaluation on identification of appropriate chronic wound models and subsequently for clinical translation. The technology developed also has application in vascularization of tissue-engineered constructs.

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