促进心脏微组织在富含 G-CSF 的胶原 I-心凝胶杂交水凝胶中组装。

IF 5.6 1区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Regenerative Biomaterials Pub Date : 2024-06-19 eCollection Date: 2024-01-01 DOI:10.1093/rb/rbae072
Hamid Khodayari, Saeed Khodayari, Malihe Rezaee, Siamak Rezaeiani, Mahmoud Alipour Choshali, Saiedeh Erfanian, Ahad Muhammadnejad, Fatemeh Nili, Yasaman Pourmehran, Reihaneh Pirjani, Sarah Rajabi, Naser Aghdami, Canan Nebigil-Désaubry, Kai Wang, Habibollah Mahmoodzadeh, Sara Pahlavan
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引用次数: 0

摘要

组织工程是生物医学的一个交叉学科,它在治疗心血管疾病和开发体外三维(3D)心脏模型方面带来了许多希望。本研究旨在使用一种富含粒细胞集落刺激因子(G-CSF)(一种源自骨髓的生长因子)的天然杂交水凝胶来设计心脏微组织。心脏 ECM 水凝胶(Cardiogel:CG)与 I 型胶原蛋白(ColI)混合形成混合水凝胶,并对其机械和生物特性进行了测试。三种细胞类型(心脏祖细胞、内皮细胞和心脏成纤维细胞)在富含 G-CSF 的混合水凝胶中共同培养,形成三维微组织。ColI 以 1:1 的比例显著改善了混合型 CG 的机械性能。混合水凝胶表现出了可接受的生物相容性,并改善了包裹人包皮成纤维细胞的保持力。与不含生长因子的混合水凝胶(对照组)相比,三种细胞类型在富含 G-CSF 的混合水凝胶中共同培养,可更快地形成三维结构和细胞化良好的微组织,并具有更高的血管生成能力。免疫染色证实了 CD31+ 管状结构以及波形蛋白+ 心脏成纤维细胞和 cTNT+ 人多能干细胞衍生心肌细胞的存在。生物信息学分析了心血管系细胞中与 G-CSF 受体相关的信号通路,确定了目标分子。与对照组相比,被硅学鉴定为参与心脏组织 G-CSF 信号转导的主要分子之一的 STAT3 在 G-CSF 中上调。富含 G-CSF 的杂交水凝胶可促进组织形成和血管生成,因此有望成为心脏组织工程的候选材料。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Promotion of cardiac microtissue assembly within G-CSF-enriched collagen I-cardiogel hybrid hydrogel.

Tissue engineering as an interdisciplinary field of biomedical sciences has raised many hopes in the treatment of cardiovascular diseases as well as development of in vitro three-dimensional (3D) cardiac models. This study aimed to engineer a cardiac microtissue using a natural hybrid hydrogel enriched by granulocyte colony-stimulating factor (G-CSF), a bone marrow-derived growth factor. Cardiac ECM hydrogel (Cardiogel: CG) was mixed with collagen type I (ColI) to form the hybrid hydrogel, which was tested for mechanical and biological properties. Three cell types (cardiac progenitor cells, endothelial cells and cardiac fibroblasts) were co-cultured in the G-CSF-enriched hybrid hydrogel to form a 3D microtissue. ColI markedly improved the mechanical properties of CG in the hybrid form with a ratio of 1:1. The hybrid hydrogel demonstrated acceptable biocompatibility and improved retention of encapsulated human foreskin fibroblasts. Co-culture of three cell types in G-CSF enriched hybrid hydrogel, resulted in a faster 3D structure shaping and a well-cellularized microtissue with higher angiogenesis compared to growth factor-free hybrid hydrogel (control). Immunostaining confirmed the presence of CD31+ tube-like structures as well as vimentin+ cardiac fibroblasts and cTNT+ human pluripotent stem cells-derived cardiomyocytes. Bioinformatics analysis of signaling pathways related to the G-CSF receptor in cardiovascular lineage cells, identified target molecules. The in silico-identified STAT3, as one of the major molecules involved in G-CSF signaling of cardiac tissue, was upregulated in G-CSF compared to control. The G-CSF-enriched hybrid hydrogel could be a promising candidate for cardiac tissue engineering, as it facilitates tissue formation and angiogenesis.

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来源期刊
Regenerative Biomaterials
Regenerative Biomaterials Materials Science-Biomaterials
CiteScore
7.90
自引率
16.40%
发文量
92
审稿时长
10 weeks
期刊介绍: Regenerative Biomaterials is an international, interdisciplinary, peer-reviewed journal publishing the latest advances in biomaterials and regenerative medicine. The journal provides a forum for the publication of original research papers, reviews, clinical case reports, and commentaries on the topics relevant to the development of advanced regenerative biomaterials concerning novel regenerative technologies and therapeutic approaches for the regeneration and repair of damaged tissues and organs. The interactions of biomaterials with cells and tissue, especially with stem cells, will be of particular focus.
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