Criticality of the biological and physical stimuli array inducing resident cardiac stem cell determination
Criticality of the biological and physical stimuli array inducing resident cardiac stem cell determination
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DOI：
10.1634/stemcells.2008-0061
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发表时间：
2008-08-01
期刊：
影响因子：
5.2
通讯作者：
Di Nardo, Paolo
中科院分区：
文献类型：
--
作者：
Forte, Giancarlo;Carotenuto, Felicia;Di Nardo, Paolo
用干细胞衍生的功能高效的心肌细胞替代受损的心肌收缩细胞被认为是退行性心脏病的根本治疗方法。然而，在心脏细胞疗法在临床实践中常规使用之前，有关分化和移植干细胞的最佳程序的许多技术问题仍有待解决。迄今为止，大多数研究都集中在评估不同生长因子的分化潜力，而没有考虑到只有生化、地形、化学和物理因素的协同配合才能诱导干细胞采取所需的表型。本研究表明，当细胞仅受到可溶性生长因子的攻击时，心脏祖细胞不会分化为心肌细胞，但需要严格控制的程序来分离祖细胞群，并人工重建微环境，该微环境的关键特征是特定生物和物理因素的微调组合。事实上，支架的几何形状和刚度对于增强生长因子对祖细胞的分化作用至关重要。这一概念的利用对于建立适当的程序来制造功能高效的工程组织至关重要。
The replacement of injured cardiac contractile cells with stem cell-derived functionally efficient cardiomyocytes has been envisaged as the resolutive treatment for degenerative heart diseases. Nevertheless, many technical issues concerning the optimal procedures to differentiate and engraft stem cells remain to be answered before heart cell therapy could tie routinely used in clinical practice. So far, most studies have been focused on evaluating the differentiative potential of different growth factors without considering that only the synergistic cooperation of biochemical, topographic, chemical, and physical factors could induce stem cells to adopt the desired phenotype. The present study demonstrates that the differentiation of cardiac progenitor cells to cardiomyocytes does not occur when cells are challenged with soluble growth factors alone, but requires strictly controlled procedures for the isolation of a progenitor cell population and the artifactual recreation of a microenvironment critically featured by a fine-tuned combination of specific biological and physical factors. Indeed, the scaffold geometry and stiffness are crucial in enhancing growth factor differentiative effects on progenitor cells. The exploitation of this concept could be essential in setting up suitable procedures to fabricate functionally efficient engineered tissues.