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用于模拟造血干细胞微环境的3D支架:应用与展望

3D Scaffolds to Model the Hematopoietic Stem Cell Niche: Applications and Perspectives.

作者信息

Congrains Ada, Bianco Juares, Rosa Renata G, Mancuso Rubia I, Saad Sara T O

机构信息

Hematology and Hemotherapy Center, Hemocentro-Unicamp, Campinas, São Paulo 13083-878, Brazil.

出版信息

Materials (Basel). 2021 Jan 26;14(3):569. doi: 10.3390/ma14030569.

Abstract

Hematopoietic stem cells (HSC) are responsible for the production of blood and immune cells during life. HSC fate decisions are dependent on signals from specialized microenvironments in the bone marrow, termed niches. The HSC niche is a tridimensional environment that comprises cellular, chemical, and physical elements. Introductorily, we will revise the current knowledge of some relevant elements of the niche. Despite the importance of the niche in HSC function, most experimental approaches to study human HSCs use bidimensional models. Probably, this contributes to the failure in translating many in vitro findings into a clinical setting. Recreating the complexity of the bone marrow microenvironment in vitro would provide a powerful tool to achieve in vitro production of HSCs for transplantation, develop more effective therapies for hematologic malignancies and provide deeper insight into the HSC niche. We previously demonstrated that an optimized decellularization method can preserve with striking detail the ECM architecture of the bone marrow niche and support HSC culture. We will discuss the potential of this decellularized scaffold as HSC niche model. Besides decellularized scaffolds, several other methods have been reported to mimic some characteristics of the HSC niche. In this review, we will examine these models and their applications, advantages, and limitations.

摘要

造血干细胞(HSC)在生命过程中负责血液和免疫细胞的生成。造血干细胞的命运决定取决于骨髓中特定微环境(称为龛)发出的信号。造血干细胞龛是一个三维环境,由细胞、化学和物理元素组成。首先,我们将回顾一下关于龛的一些相关元素的当前知识。尽管龛在造血干细胞功能中很重要,但大多数研究人类造血干细胞的实验方法都使用二维模型。这可能导致许多体外研究结果无法转化为临床应用。在体外重建骨髓微环境的复杂性将为实现用于移植的造血干细胞的体外生产、开发更有效的血液系统恶性肿瘤治疗方法以及更深入地了解造血干细胞龛提供一个强大的工具。我们之前证明,一种优化的脱细胞方法可以极其详细地保留骨髓龛的细胞外基质(ECM)结构并支持造血干细胞培养。我们将讨论这种脱细胞支架作为造血干细胞龛模型的潜力。除了脱细胞支架外,还报道了其他几种方法来模拟造血干细胞龛的一些特征。在这篇综述中,我们将研究这些模型及其应用、优点和局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ff7/7865713/e95571860c65/materials-14-00569-g001.jpg

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