丝基基质和c- kit阳性心脏祖细胞用于细胞化丝素蛋白支架:体内模型的研究。

IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Antonella Motta, Rosario Barone, Filippo Macaluso, Filippo Giambalvo, Francesco Pecoraro, Patrizia Di Marco, Giovanni Cassata, Roberto Puleio, Claudio Migliaresi, Annalisa Guercio, Valentina Di Felice
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引用次数: 4

摘要

细胞化丝素蛋白支架的生产是非常困难的,因为实际上不可能将细胞分化成组织良好的心脏组织。没有血管化,细胞团不仅不能生长,而且可能出现坏死,这表明缺氧和缺乏营养。在本研究中,我们使用酪氨酸蛋白激酶试剂盒(c-Kit)阳性的心脏祖细胞(CPCs)来生成心脏细胞化的丝素蛋白支架,这是迄今为止从成人心脏中分离出来的多能细胞,可以向心脏表型表现出一定程度的分化。为了检测它们在体内向心脏表型分化的能力,我们将CPC和胶原蛋白类器官样团块植入裸鼠体内,观察它们的行为。由于支架可以保留心脏组织的三维结构,我们平行制备了3种不同几何形状的丝素蛋白支架,并在3种不同的免疫抑制动物模型中测试了它们的行为。不幸的是,CPC细胞化丝素蛋白支架不能在体内使用。单独植入或在I型胶原凝胶中植入的CPCs被CD3+淋巴细胞聚集体破坏,而多孔和部分定向的支架则引发了以巨细胞为特征的一致的异物反应。只有静电纺网对异物反应有抵抗作用。综上所述,c- kit阳性的心肌细胞虽然在体外有或没有丝素网片的情况下表达了良好水平的心脏分化标志物,但不适合用于心脏类器官的体内模型,因为它们会被t细胞介导的免疫反应降解。即使支架可以保持这些细胞在体内的存活,也会引起宿主反应。然而,在测试的支架中,与所有其他测试结构相比,静电纺网(F-scaffold)诱导的响应较低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Silk-Based Matrices and c-Kit-Positive Cardiac Progenitor Cells for a Cellularized Silk Fibroin Scaffold: Study of an in vivo Model.

The production of a cellularized silk fibroin scaffold is very difficult because it is actually impossible to differentiate cells into a well-organized cardiac tissue. Without vascularization, not only do cell masses fail to grow, but they may also exhibit an area of necrosis, indicating a lack of oxygen and nutrients. In the present study, we used the so-called tyrosine protein kinase kit (c-Kit)-positive cardiac progenitor cells (CPCs) to generate cardiac cellularized silk fibroin scaffolds, multipotent cells isolated from the adult heart to date that can show some degree of differentiation toward the cardiac phenotype. To test their ability to differentiate into the cardiac phenotype in vivo as well, CPC and collagen organoid-like masses were implanted into nude mice and their behavior observed. Since the 3-dimensional structure of cardiac tissue can be preserved by scaffolds, we prepared in parallel different silk fibroin scaffolds with 3 different geometries and tested their behavior in 3 different models of immunosuppressed animals. Unfortunately, CPC cellularized silk fibroin scaffolds cannot be used in vivo. CPCs implanted alone or in collagen type I gel were destroyed by CD3+ lymphocyte aggregates, whereas the porous and partially oriented scaffolds elicited a consistent foreign body response characterized by giant cells. Only the electrospun meshes were resistant to the foreign body reaction. In conclusion, c-Kit-positive CPCs, although expressing a good level of cardiac differentiation markers in vitro with or without fibroin meshes, are not suitable for an in vivo model of cardiac organoids because they are degraded by a T-cell-mediated immune response. Even scaffolds which may preserve the survival of these cells in vivo also induced a host response. However, among the tested scaffolds, the electrospun meshes (F-scaffold) induced a lower response compared to all the other tested structures.

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来源期刊
Cells Tissues Organs
Cells Tissues Organs 生物-发育生物学
CiteScore
4.90
自引率
3.70%
发文量
45
审稿时长
6-12 weeks
期刊介绍: ''Cells Tissues Organs'' aims at bridging the gap between cell biology and developmental biology and the emerging fields of regenerative medicine (stem cell biology, tissue engineering, artificial organs, in vitro systems and transplantation biology). CTO offers a rapid and fair peer-review and exquisite reproduction quality. Special topic issues, entire issues of the journal devoted to a single research topic within the range of interests of the journal, are published at irregular intervals.
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