Fusing Tissue Engineering and Systems Biology Toward Fulfilling Their Promise

Fusing Tissue Engineering and Systems Biology Toward Fulfilling Their Promise
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DOI:
10.1007/s12195-008-0007-9
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发表时间:
2008-03-01
影响因子:
2.8
通讯作者:
Lauffenburger, Douglas A.
Lauffenburger, Douglas A.
中科院分区:
工程技术4区
文献类型:
--
作者:
Cosgrove, Benjamin D.;Griffith, Linda G.;Lauffenburger, Douglas A.

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组织工程学已经取得了进展,能够通过控制各种微环境设计特征,包括机械、细胞外基质和可溶刺激线索,来开发能够概括体内细胞生理的工程化3D体外组织模型。微环境线索通过一个相互关联的分子调控通路系统刺激细胞,这些调控通路控制着工程化组织模型中的细胞行为。详细了解细胞信号通路如何处理这些微环境刺激以控制它们的行为,将需要应用系统级生物学方法。到目前为止,系统生物学核心的实验和建模方法在很大程度上是在相对简单的、容易和重复寻址的实验环境中进行检验的,例如2D培养中的哺乳动物细胞系。为了增强系统生物学对人类生理和疾病潜在的复杂细胞过程的洞察,并确定和验证候选治疗方法的前景,需要将其推进到更有效地代表天然组织的复杂性和功能的改进的实验环境中。在这里,我们讨论了系统生物学如何适应组织工程的实验限制和兴趣,并建议系统生物学如何帮助设计和研究用于人类生理学和病理生理学研究的工程化组织模型。
Tissue engineering has progressed to enable development of engineered 3D in vitro tissue models that can recapitulate in vivo cellular physiologies through the control of an expansive variety of microenvironmental design features, including mechanical, extracellular matrix, and soluble stimulatory cues. Microenviromental cues stimulate cells through a system of interconnected molecular regulatory pathways that govern cellular behaviors within engineered tissue models. Detailed understanding of how cell signaling pathways process these microenvironmental stimuli to govern their behaviors will require application of systems-level biological approaches. To date, the experimental and modeling approaches at the heart of systems biology have largely been examined in relatively simple experimental contexts that are readily and repeatedly addressable, such as mammalian cell lines in 2D culture. To enhance the prospects for systems biology to bring about insight into the complex cellular processes underlying human physiology and disease, and to identify and validate candidate therapeutic approaches, it needs to be advanced into improved experimental contexts that more effectively represent the complexity and functionality of native tissues. Herein, we discuss how systems biology can be adapted to the experimental constraints and interests of tissue engineering, and suggest how systems biology could aid in designing and investigating engineered tissue models for the study of human physiology and pathophysiology.