A 3-D cardiac muscle construct for exploring adult marrow stem cell based myocardial regeneration.
A 3-D cardiac muscle construct for exploring adult marrow stem cell based myocardial regeneration.
复制标题
用于探索基于成体骨髓干细胞的心肌再生的 3-D 心肌结构。
DOI：
10.1016/j.biomaterials.2010.01.041
复制
发表时间：
2010
期刊：
影响因子：
14
通讯作者：
Potts,JayD
中科院分区：
文献类型：
--
作者：
Valarmathi,ManiT;Goodwin,RichardL;Fuseler,JohnW;Davis,JeffreyM;Yost,MichaelJ;Potts,JayD
成人骨髓基质细胞（BMSCs）在体外可分化为心肌样细胞，在体内可促进心肌再生。因此，骨髓间充质干细胞可能在心脏修复和再生中发挥重要作用。然而，这一概念受到BMSC向心肌细胞分化不充分和不一致的限制，沿着，植入缺血心肌后新生心肌细胞的存活和整合较差。为了克服这些障碍，并探讨成人干细胞为基础的心肌再生，我们已经开发了一种体外模型的三维（3-D）心肌使用大鼠心室胚胎心肌细胞（ECM）和骨髓间充质干细胞。当将ECM和BMSC依次接种到由拓扑排列的I型胶原纤维工程化的3-D管状支架上并在基础培养基中培养7、14、21或28天时，观察到成熟和共分化成心肌细胞谱系。从形态学、免疫学、生物化学和分子水平对表型诱导进行了表征。所观察到的心肌细胞表型标记物编码的转录本的表达和心肌细胞谱系相关蛋白的免疫定位揭示了新心肌形成的典型表达模式。在生化水平上，分化细胞表现出适当的代谢活性，在超微结构水平上，肌原纤维和肌节组织是不成熟表型的指示。我们的3-D共培养系统维持ECM在体外的连续分化过程，同时诱导BMSCs成熟和分化为心肌样细胞。因此，这种新的3-D共培养系统提供了一个有用的体外模型，以研究在心肌分化过程中发育中的ECM和BMSCs的功能作用和相互作用。
Adult bone marrow stromal cells (BMSCs) are capable of differentiating into cardiomyocyte-like cells in vitro and contribute to myocardial regeneration in vivo. Consequently, BMSCs may potentially play a vital role in cardiac repair and regeneration. However, this concept has been limited by inadequate and inconsistent differentiation of BMSCs into cardiomyocytes along with poor survival and integration of neo-cardiomyocytes after implantation into ischemic myocardium. In order to overcome these barriers and to explore adult stem cell based myocardial regeneration, we have developed an in vitro model of three-dimensional (3-D) cardiac muscle using rat ventricular embryonic cardiomyocytes (ECMs) and BMSCs. When ECMs and BMSCs were seeded sequentially onto a 3-D tubular scaffold engineered from topographically aligned type I collagen-fibers and cultured in basal medium for 7, 14, 21, or 28 days, the maturation and co-differentiation into a cardiomyocyte lineage was observed. Phenotypic induction was characterized at morphological, immunological, biochemical and molecular levels. The observed expression of transcripts coding for cardiomyocyte phenotypic markers and the immunolocalization of cardiomyogenic lineage-associated proteins revealed typical expression patterns of neo-cardiomyogenesis. At the biochemical level differentiating cells exhibited appropriate metabolic activity and at the ultrastructural level myofibrillar and sarcomeric organization were indicative of an immature phenotype. Our 3-D co-culture system sustains the ECMs in vitro continuum of differentiation process and simultaneously induces the maturation and differentiation of BMSCs into cardiomyocyte-like cells. Thus, this novel 3-D co-culture system provides a useful in vitro model to investigate the functional role and interplay of developing ECMs and BMSCs during cardiomyogenic differentiation.
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可塑性的强度：用于心脏修复的干细胞。
影响因子：
3.5
作者：
D. Orlic
通讯作者：
D. Orlic
DOI：
10.1172/jci14327c1
发表时间：
2002-02
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Morayma Reyes;Arkadiusz Dudek;B. Jahagirdar;L. Koodie;P. Marker;Catherine M. Verfaillie
通讯作者：
Morayma Reyes;Arkadiusz Dudek;B. Jahagirdar;L. Koodie;P. Marker;Catherine M. Verfaillie
影响因子：
2.4
作者：
Fukuda, K
通讯作者：
Fukuda, K
胚胎干细胞衍生的胚体中心血管系统的发育
DOI：
--
发表时间：
2004
期刊：
影响因子：
--
作者：
H. Sauer;M. Wartenberg;A. Sachinidis;J. Hescheler
通讯作者：
J. Hescheler
影响因子：
15.9
作者：
Jackson, KA;Majka, SM;Goodell, MA
通讯作者：
Goodell, MA