Dynamic alterations of metabolites revealed the vascularization progression of bioengineered liver

脐静脉 代谢组学 去细胞化 体外 生物 代谢物 生物化学 化学 细胞生物学 生物信息学 细胞外基质
作者
Qian Zhou,Beibei Guo,Deying Chen,Heng Yao,Xi Liang,Jiaojiao Xin,Dongyan Shi,Keke Ren,Hui Yang,Jing Jiang,­Jun Li­
出处
期刊:Biotechnology and Bioengineering [Wiley]
卷期号:119 (10): 2857-2867 被引量:1
标识
DOI:10.1002/bit.28189
摘要

Vascularization is a critical but challenging process in developing functional bioengineered livers with the decellularized liver scaffolds (DLSs) and the process is accompanied by cell-specific metabolic alterations. To elucidate the dynamic alterations of metabolites during vascularization, rat DLSs were vascularized with human umbilical vein endothelial cells and liquid chromatography mass spectrometry-based metabolomics was performed on culture supernatants collected at 0, 1, 3, 7, 14, and 21 days. Overall, 1698 peak pairs or metabolites were detected in the culture supernatants, with 309 metabolites being positively identified. The orthogonal partial least-squares discriminant analysis and functional enrichment analysis revealed three phases that could be clearly discriminated, including Phase D1 (cell proliferation and migration), Phase D3D7 (vascular lumen formation), and Phase D14D21 (functional endothelial barrier formation). Seventy-two common differentially abundant metabolites of known identity were detected in these three phases when compared with Day 0. Of these metabolites, a high level of β-Alanine indicated a better degree of vascularization and 14 days of in vitro dynamic culture is required to develop a functionalized vascular structure. These results enriched our understanding of the metabolic mechanism of DLS vascularization and indicated that β-Alanine could function as a potential predictor of the patency of vascularized bioengineered livers.
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