Mahara Atsushi, Shirai Manabu, Soni Raghav, Le Hue Thi, Shimizu Kaito, Hirano Yoshiaki, Yamaoka Tetsuji
Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Kishibe Shimmachi, Suita Osaka, 564-8565, Japan.
Omics Research Center, National Cerebral and Cardiovascular Center Research Institute, Kishibe Shimmachi, Suita Osaka, 564-8565, Japan.
Mater Today Bio. 2023 Oct 28;23:100847. doi: 10.1016/j.mtbio.2023.100847. eCollection 2023 Dec.
Although the clinical application of cell-free tissue-engineered vascular grafts (TEVGs) has been proposed, vascular tissue regeneration mechanisms have not been fully clarified. Here, we report that monocyte subpopulations reconstruct vascular-like tissues through integrin signaling. An Arg-Glu-Asp-Val peptide-modified acellular long-bypass graft was used as the TEVG, and tissue regeneration in the graft was evaluated using a cardiopulmonary pump system and porcine transplantation model. In 1 day, the luminal surface of the graft was covered with cells that expressed CD163, CD14, and CD16, which represented the monocyte subpopulation, and they exhibited proliferative and migratory abilities. RNA sequencing showed that captured cells had an immune-related phenotype similar to that of monocytes and strongly expressed cell adhesion-related genes. In vitro angiogenesis assay showed that tube formation of the captured cells occurred via integrin signal activation. After medium- and long-term graft transplantation, the captured cells infiltrated the tunica media layer and constructed vascular with a CD31/CD105-positive layer and an αSMA-positive structure after 3 months. This finding, including multiple early-time observations provides clear evidence that blood-circulating monocytes are directly involved in vascular remodeling.
尽管无细胞组织工程血管移植物（TEVGs）的临床应用已被提出，但其血管组织再生机制尚未完全阐明。在此，我们报告单核细胞亚群通过整合素信号通路重建类血管组织。将一种精氨酸-谷氨酸-天冬氨酸-缬氨酸肽修饰的脱细胞长旁路移植物用作TEVG，并使用心肺泵系统和猪移植模型评估移植物中的组织再生。在1天时，移植物的管腔表面覆盖有表达CD163、CD14和CD16的细胞，这些细胞代表单核细胞亚群，并且它们表现出增殖和迁移能力。RNA测序显示，捕获的细胞具有与单核细胞相似的免疫相关表型，并强烈表达细胞黏附相关基因。体外血管生成试验表明，捕获细胞的管腔形成是通过整合素信号激活发生的。在中长期移植物移植后，捕获的细胞浸润到中膜层，并在3个月后构建出具有CD31/CD105阳性层和αSMA阳性结构的血管。这一发现，包括多个早期观察结果，提供了明确的证据表明血液循环中的单核细胞直接参与血管重塑。
