کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6449695 1415936 2017 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Full length articleEngineered extracellular microenvironment with a tunable mechanical property for controlling cell behavior and cardiomyogenic fate of cardiac stem cells
ترجمه فارسی عنوان
مقاله کامل مقاله میکرو محیط زیست خارج سلولی را با یک ویژگی مکانی قابل تنظیم برای کنترل رفتار سلولی و سرنوشت قلب و عروق سلول های بنیادی قلب
کلمات کلیدی
سلول های بنیادی قلب، میکرو محیط، مدول الاستیک رفتار سلولی، سرنوشت قلب و عروق،
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
چکیده انگلیسی

Endogenous cardiac stem cells (CSCs) are known to play a certain role in the myocardial homeostasis of the adult heart. The extracellular matrix (ECM) surrounding CSCs provides mechanical signals to regulate a variety of cell behaviors, yet the impact in the adult heart of these mechanical properties of ECM on CSC renewal and fate decisions is mostly unknown. To elucidate CSC mechanoresponses at the individual cell and myocardial level, we used the sol-to-gel transitional gelatin-poly(ethylene glycol)-tyramine (GPT) hydrogel with a tunable mechanical property to construct a three-dimensional (3D) matrix for culturing native myocardium and CSCs. The elastic modulus of the GPT hydrogel was controlled by adjusting cross-linking density using hydrogen peroxide. The GPT hydrogel showed an ability to transduce integrin-mediated signals into the myocardium and to permit myocardial homeostatic processes in vitro, including CSC migration and proliferation into the hydrogel from the myocardium. Decreasing the elastic modulus of the hydrogel resulted in upregulation of phosphorylated integrin-mediated signaling molecules in CSCs, which were associated with significant increases in cell spreading, migration, and proliferation of CSCs in a modulus-dependent manner. However, increasing the elastic modulus of hydrogel induced the arrest of cell growth but led to upregulation of cardiomyocyte-associated mRNAs in CSCs. This work demonstrates that tunable 3D-engineered microenvironments created by GPT hydrogel are able to control CSC behavior and to direct cardiomyogenic fate. Our system may also be appropriate for studying the mechanoresponse of CSCs in a 3D context as well as for developing therapeutic strategies for in situ myocardial regeneration.Statement of SignificanceThe extracellular matrix (ECM) provides a physical framework of myocardial niches in which endogenous cardiac stem cells (CSCs) reside, renew, differentiate, and replace cardiac cells. Interactions between ECM and CSCs might be critical for the maintenance of myocardial homeostasis in the adult heart. Yet most studies done so far have used irrelevant cell types and have been performed at the individual cell level, none able to reflect the in vivo situation. By the use of a chemically defined hydrogel to create a tunable 3D microenvironment, we succeeded in controlling CSC behavior at the myocardial and individual cell level and directing the cardiomyogenic fate. Our work may provide insight into the design of biomaterials for in situ myocardial regeneration as well as for tissue engineering.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Acta Biomaterialia - Volume 50, 1 March 2017, Pages 234-248
نویسندگان
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