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发育起源、微环境力学及氧供应对间充质干/基质细胞成骨分化能力的影响

Impact of developmental origin, niche mechanics and oxygen availability on osteogenic differentiation capacity of mesenchymal stem/stromal cells.

作者信息

Bryniarska Natalia, Kubiak Andrzej, Łabędź-Masłowska Anna, Zuba-Surma Ewa

机构信息

1Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland; 2Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

1Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland; 2Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

出版信息

Acta Biochim Pol. 2019 Dec 29;66(4):491-498. doi: 10.18388/abp.2019_2893.

DOI:10.18388/abp.2019_2893
PMID:31883439
Abstract

Mesenchymal Stem/Stromal Cells (MSCs) have been widely considered as a promising source of cells for tissue regeneration. Among other stem cells, they are characterized by a high osteogenic potential. Intensive studies in this field had shown that even if basic osteogenic differentiation is relatively simple, its clinical application requires more sophisticated approaches to prepare effective and safe cell therapy products. The aim of this review is to underline biological, physical and chemical factors which play a crucial role in osteogenic differentiation of MSCs. Existence of two distinct mechanisms of ossification (intramembranous and endochondral) indicate that choosing a proper source of MSCs may be critical for successful regeneration of a particular bone type. In this context, Dental Pulp Stem Cells representing a group of MSCs and originating from neural crest ( a structure responsible for development of cranial bones) are considered as the most promising for skull bone defect repair. Factors which facilitate osteogenic differentiation of MSCs include changes in forces exerted on cells during development. Thus, culturing of cells in hydrogels or on biocompatible three-dimensional scaffolds improves osteogenic differentiation of MSCs by both, the mechanotransductive and chemical impact on cells. Moreover, atmospheric oxygen concentration routinely used for cell cultures in vitro does not correspond to lower oxygen concentration present in stem cell niches. A decrease in oxygen concentration allows to create more physiological cell culture conditions, mimicking the ones in stem cell niches, which promote the MSCs stemness. Altogether, factors discussed in this review provide exciting opportunities to boost MSCs propagation and osteogenic differentiation which is crucial for successful clinical applications.

摘要

间充质干/基质细胞(MSCs)已被广泛认为是组织再生中一种很有前景的细胞来源。在其他干细胞中,它们具有很高的成骨潜能。该领域的深入研究表明,即使基本的成骨分化相对简单,其临床应用也需要更复杂的方法来制备有效且安全的细胞治疗产品。本综述的目的是强调在MSCs成骨分化中起关键作用的生物学、物理和化学因素。两种不同的骨化机制(膜内骨化和软骨内骨化)的存在表明,选择合适的MSCs来源对于特定骨类型的成功再生可能至关重要。在这种情况下,牙髓干细胞作为MSCs的一个群体,起源于神经嵴(一种负责颅骨发育的结构),被认为是颅骨缺损修复最有前景的细胞来源。促进MSCs成骨分化的因素包括发育过程中施加在细胞上的力的变化。因此,在水凝胶中或生物相容性三维支架上培养细胞,通过对细胞的机械转导和化学影响,改善了MSCs的成骨分化。此外,体外细胞培养常规使用的大气氧浓度与干细胞微环境中较低的氧浓度不相符。降低氧浓度可以创造更接近生理状态的细胞培养条件,模拟干细胞微环境中的条件,从而促进MSCs的干性。总之,本综述中讨论的因素为促进MSCs的增殖和成骨分化提供了令人兴奋的机会,这对于成功的临床应用至关重要。

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