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富马酸二甲酯预处理可通过增强营养因子谱来增强骨髓间充质干细胞的治疗潜力。

Dimethyl Fumarate Preconditioning can Reinforce the Therapeutic Potential of Bone Marrow Mesenchymal Stem Cells through Trophic Factor Profile Enhancement.

作者信息

Pandamooz Sareh, Safari Anahid, Ghorbani Nasrin, Jamhiri Iman, Zare Shahrokh, Belém-Filho Ivaldo Jesus Almeida, Dolati Parisa, Salehi Mohammad Saied

机构信息

Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Nursing, College of Nursing, Lebanese French University, Erbil, Kurdistan, Iraq.

出版信息

Adv Biomed Res. 2024 Jul 29;13:37. doi: 10.4103/abr.abr_298_23. eCollection 2024.

DOI:10.4103/abr.abr_298_23
PMID:39224404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11368223/
Abstract

BACKGROUND

Numerous studies have confirmed the therapeutic efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in addressing neurologic disorders. To date, several preconditioning strategies have been designed to improve the therapeutic potential of these stem cells. This study was designed to evaluate the preconditioning effect of dimethyl fumarate (DMF) on the expression of main trophic factors in human BM-MSCs.

MATERIALS AND METHODS

Initially, the identity of stem cells was confirmed through the evaluation of surface markers and their capacity for osteogenic and adipogenic differentiation using flow cytometry and differentiation assay, respectively. Subsequently, stem cells were subjected to different concentrations of DMF for 72 hours and their viability was defined by MTT assay. Following 72-hour preconditioning period with 10 µM DMF, gene expression was assessed by quantitative RT-PCR.

RESULTS

Our findings demonstrated that the isolated stem cells expressed cardinal MSC surface markers and exhibited osteogenic and adipogenic differentiation potential. MTT results confirmed that 10 µM DMF was an optimal dose for maintaining cell viability. Preconditioning of stem cells with DMF significantly upregulated the expression of , , and . Despite a slight increase in transcript level of and after DMF preconditioning, this difference was not statistically significant.

CONCLUSIONS

Our findings suggest that DMF preconditioning can enhance the expression of major neurotrophic factors in human BM-MSCs. Given the curative potential of both BM-MSCs and DMF in various neurological disease models and preconditioning outcomes, their combined use may synergistically enhance their neuroprotective properties.

摘要

背景

众多研究已证实骨髓间充质干细胞(BM-MSCs)在治疗神经系统疾病方面的疗效。迄今为止,已设计了几种预处理策略来提高这些干细胞的治疗潜力。本研究旨在评估富马酸二甲酯(DMF)对人BM-MSCs中主要营养因子表达的预处理效果。

材料与方法

首先,通过分别使用流式细胞术和分化试验评估表面标志物及其成骨和成脂分化能力来确认干细胞的身份。随后,将干细胞用不同浓度的DMF处理72小时,并通过MTT试验确定其活力。在用10μM DMF预处理72小时后,通过定量RT-PCR评估基因表达。

结果

我们的研究结果表明,分离出的干细胞表达主要的间充质干细胞表面标志物,并表现出成骨和成脂分化潜力。MTT结果证实10μM DMF是维持细胞活力的最佳剂量。用DMF对干细胞进行预处理可显著上调 、 和 的表达。尽管DMF预处理后 和 的转录水平略有增加,但这种差异无统计学意义。

结论

我们的研究结果表明,DMF预处理可增强人BM-MSCs中主要神经营养因子的表达。鉴于BM-MSCs和DMF在各种神经疾病模型中的治疗潜力以及预处理结果,它们的联合使用可能会协同增强其神经保护特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/8a034225b472/ABR-13-37-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/56706ac9d904/ABR-13-37-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/6c6f1686a990/ABR-13-37-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/431271f320c8/ABR-13-37-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/1d7bb3c16eb2/ABR-13-37-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/f7eca1472bf2/ABR-13-37-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/8a034225b472/ABR-13-37-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/56706ac9d904/ABR-13-37-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/6c6f1686a990/ABR-13-37-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/431271f320c8/ABR-13-37-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/1d7bb3c16eb2/ABR-13-37-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/f7eca1472bf2/ABR-13-37-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3a/11368223/8a034225b472/ABR-13-37-g006.jpg

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