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三维基质中的人类心脏多能成体干细胞:心肌梗死后心脏再生组织工程的新方法。

Human cardiac multipotent adult stem cells in 3D matrix: new approach of tissue engineering in cardiac regeneration post-infarction.

作者信息

Di Spigna G, Iannone M, Ladogana P, Salzano S, Ventre M, Covelli B, De Marinis E, Postiglione L

机构信息

Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy.

Interdisciplinary Research Centre on Biomaterials. Department of Chemical, Materials and Industrial Production Engineering, University of Naples “Federico II”, Italy.

出版信息

J Biol Regul Homeost Agents. 2017 Oct-Dec;31(4):911-921.

PMID:29254293
Abstract

Myocardial infarction is the leading cause of morbidity and mortality in developed countries. It causes a left ventricular dysfunction, mainly due to the loss of functional tissue, resulting in heart failure. New therapies are being developed, using a tissue engineering approach, with the ultimate goal of restoring cardiac function by regenerating and repairing the damaged myocardium. In the present study we investigated the behaviour of a specific population of c-kit positive human cardiac stem cells, called Multipotent Adult Stem Cells (MASCs), grown within three-dimensional collagen scaffolds (3D), to establish whether they could be used in post-infarction cardiac regeneration. We also evaluated the expression levels of the Granulocyte Macrophage-Colony Stimulating Factor Receptor (GM-CSFR) and endoglin, a component of the Transforming Growth Factor beta (TGF-ß) receptor complex. Finally, we also evaluated the expression of the α2β1integrin. MASCs cultured within 3D collagen matrices are able to proliferate and migrate even in the absence of chemotactic agents and express high levels of factors involved in cell proliferation and migration, such as GM-CSFRα chain and integrins. They therefore represent a promising approach to tissue engineering aimed to restore cardiac function. Our results also suggest a role of GM-CSF in cell proliferation, while TGF-β does not seem to be relevant.

摘要

心肌梗死是发达国家发病和死亡的主要原因。它会导致左心室功能障碍,主要是由于功能性组织的丧失,进而引发心力衰竭。目前正在采用组织工程方法开发新的治疗方法,其最终目标是通过再生和修复受损心肌来恢复心脏功能。在本研究中,我们调查了一种特定的c-kit阳性人类心脏干细胞群体,即多能成体干细胞(MASC),在三维胶原支架(3D)内生长的行为,以确定它们是否可用于心肌梗死后的心脏再生。我们还评估了粒细胞巨噬细胞集落刺激因子受体(GM-CSFR)和内皮糖蛋白(一种转化生长因子β(TGF-β)受体复合物的成分)的表达水平。最后,我们还评估了α2β1整合素的表达。在3D胶原基质中培养的MASC即使在没有趋化剂的情况下也能够增殖和迁移,并表达高水平的参与细胞增殖和迁移的因子,如GM-CSFRα链和整合素。因此,它们代表了一种有前景的组织工程方法,旨在恢复心脏功能。我们的结果还表明GM-CSF在细胞增殖中起作用,而TGF-β似乎无关。

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J Cardiovasc Transl Res. 2022 Feb;15(1):179-203. doi: 10.1007/s12265-021-10154-4. Epub 2021 Aug 3.
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Growth Factor Gene-Modified Mesenchymal Stem Cells in Tissue Regeneration.生长因子基因修饰间充质干细胞在组织再生中的作用。
Drug Des Devel Ther. 2020 Mar 26;14:1241-1256. doi: 10.2147/DDDT.S243944. eCollection 2020.
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Comparison of biological characteristics of mesenchymal stem cells derived from the human umbilical cord and decidua parietalis.
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Mol Med Rep. 2019 Jul;20(1):633-639. doi: 10.3892/mmr.2019.10286. Epub 2019 May 23.
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Collagen biomaterial for the treatment of myocardial infarction: an update on cardiac tissue engineering and myocardial regeneration.胶原生物材料治疗心肌梗死:心脏组织工程和心肌再生的最新进展。
Drug Deliv Transl Res. 2019 Oct;9(5):920-934. doi: 10.1007/s13346-019-00627-0.