Ort Carley, Dayekh Khalil, Xing Malcolm, Mequanint Kibret
Department of Mechanical Engineering, University of Manitoba, 66 Chancellors Circle, Winnipeg R3T 2N2, Canada.
ACS Biomater Sci Eng. 2018 Nov 12;4(11):3644-3657. doi: 10.1021/acsbiomaterials.8b00532. Epub 2018 Aug 20.
Stem cells have transformed the fields of tissue engineering and regenerative medicine, and their potential to further advance these fields cannot be overstated. The stem cell niche is a dynamic microenvironment that determines cell fate during development and tissue repair following an injury. Classically, stem cells were studied in isolation of their microenvironment; however, contemporary research has produced a myriad of evidence that shows the importance of multiple aspects of the stem cell niche in regulating their processes. In the context of tissue engineering and regenerative medicine studies, the niche is an artificial environment provided by culture conditions. In vitro culture conditions may involve coculturing with other cell types, developing specific biomaterials, and applying relevant forces to promote the desired lineage commitment. Considerable advance has been made over the past few years toward directed stem cell differentiation; however, the unspecific differentiation of stem cells yielding a mixed population of cells has been a challenge. In this review, we provide a systematic review of the emerging strategies used for lineage commitment within the context of tissue engineering and regenerative medicine. These strategies include scaffold pore-size and pore-shape gradients, stress relaxation, sonic and electromagnetic effects, and magnetic forces. Finally, we provide insights and perspectives into future directions focusing on signaling pathways activated during lineage commitment using external stimuli.
干细胞已经改变了组织工程和再生医学领域,而且它们进一步推动这些领域发展的潜力再怎么强调也不为过。干细胞生态位是一个动态的微环境,它在发育过程以及损伤后的组织修复过程中决定细胞命运。传统上,干细胞是在脱离其微环境的情况下进行研究的;然而,当代研究已经产生了大量证据,表明干细胞生态位的多个方面在调节其过程中的重要性。在组织工程和再生医学研究的背景下,生态位是由培养条件提供的人工环境。体外培养条件可能涉及与其他细胞类型共培养、开发特定的生物材料以及施加相关力以促进所需的谱系定向分化。在过去几年中,在定向干细胞分化方面已经取得了相当大的进展;然而,干细胞的非特异性分化产生混合细胞群体一直是一个挑战。在这篇综述中,我们对组织工程和再生医学背景下用于谱系定向分化的新兴策略进行了系统综述。这些策略包括支架孔径和孔形状梯度、应力松弛、声波和电磁效应以及磁力。最后,我们针对未来方向提供了见解和观点,重点关注使用外部刺激在谱系定向分化过程中激活的信号通路。