Reconstruction of bone marrow microenvironment for expansion of hematopoietic stem cells by a histone deacetylase inhibitor.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2023-06-01 Epub Date: 2023-04-07 DOI:10.1007/s10616-022-00564-w

Maryam Haj Ali Askari, Majid Shahabi, Amir Asri Kojabad, Mahin Nikougoftar Zarif

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引用次数: 0

Abstract

Ex vivo expansion of hematopoietic stem cells (HSCs) is an approach for overcoming cell insufficiency for umbilical cord blood transplantation. It was suggested that in common ex vivo cultures, the stemness specificity of HSCs is rapidly reducing due to DNA hypermethylation. Here, Nicotinamide (NAM), a DNA methyltransferase and histone deacetylase inhibitor, is used with a bioengineered Bone Marrow-like niche (BLN) for HSC ex vivo expansion. The CFSE cell proliferation assay was used for tracking HSCs division. qRT-PCR was conducted to assay the HOXB4 mRNA expression levels. The morphology of BLN-cultured cells was analyzed using scanning electron microscopy (SEM). NAM boosted the induction of HSC proliferation in the BLN group compared to the control group. In addition, the ability of HSCs to colonize was more significant in the BLN group than in the control group. Our data suggest that the presence of NAM in bioengineered niches promotes HSC proliferation. The presented approach showed that small molecules could be used in the clinical setting to overcome the limited number of CD34⁺ cells in cord blood units.

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组蛋白去乙酰化酶抑制剂重建骨髓微环境以扩增造血干细胞。

造血干细胞（HSCs）的离体扩增是克服脐带血移植中细胞不足的一种方法。有人认为，在常见的离体培养中，由于DNA超甲基化，HSC的干性特异性正在迅速降低。在这里，烟酰胺（NAM），一种DNA甲基转移酶和组蛋白脱乙酰酶抑制剂，与生物工程骨髓样小生境（BLN）一起用于HSC的离体扩增。CFSE细胞增殖测定用于追踪HSC分裂。qRT-PCR检测HOXB4mRNA的表达水平。用扫描电子显微镜（SEM）分析BLN培养细胞的形态。与对照组相比，NAM促进了BLN组HSC增殖的诱导。此外，BLN组的HSC定植能力比对照组更显著。我们的数据表明，NAM在生物工程小生境中的存在促进了HSC的增殖。所提出的方法表明，小分子可以在临床环境中用于克服脐血单位中CD34+细胞数量有限的问题。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.