Functionally improved mesenchymal stem cells via nanosecond pulsed electric fields for better treatment of osteoarthritis

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Abstract

Background

Numerous approaches have been utilized to optimize mesenchymal stem cells (MSCs) performance in treating osteoarthritis (OA), however, the constrained diminished activity and chondrogenic differentiation capacity impede their therapeutic efficacy. Previous investigations have successfully shown that pretreatment with nanosecond pulsed electric fields (nsPEFs) significantly enhances the chondrogenic differentiation of MSCs. Therefore, this study aims to explore nsPEFs as a strategy to improve OA therapy by enhancing MSCs' activity and chondrogenic differentiation and also investigate its potential mechanism.

Methods

In this study, a million MSCs were carefully suspended within a 0.4-cm gap cuvette and subjected to five pulses of nsPEFs (100 ns at 10 kV/cm, 1 Hz), with a 1-s interval between each pulse. A control group of MSCs was maintained without nsPEFs treatment for comparative analysis. nsPEFs were applied to regulate the MSCs performance and hinder OA progresses. In order to further explore the corresponding mechanism, we examined the changes of MSCs transcriptome after nsPEF pretreatment. Finally, we studied the properties of extracellular vesicles (EVs) secreted by MSCs affected by nsPEF and the therapeutic effect on OA.

Results

We found that nsPEFs pretreatment promoted MSCs migration and viability, particularly enhancing their viability temporarily in vivo, which is also confirmed by mRNA sequencing analysis. It also significantly inhibited the development of OA-like chondrocytes in vitro and prevented OA progression in rat models. Additionally, we discovered that nsPEFs pretreatment reprogrammed MSC performance by enhancing EVs production (5.77 ± 0.92 folds), and consequently optimizing their therapeutic potential.

Conclusions

In conclusion, nsPEFs pretreatment provides a simple and effective strategy for improving the MSCs performance and the therapeutic effects of MSCs for OA. EVs-nsPEFs may serve as a potent therapeutic material for OA and hold promise for future clinical applications.

The translational potential of this article

This study indicates that MSCs pretreated by nsPEFs greatly inhibited the development of OA. nsPEFs pretreatment will be a promising and effective method to optimize the therapeutic effect of MSCs in the future.

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Most cited references 44

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Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

Yingyao Zhou, Bin Zhou, Lars Pache … (2019)

A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets. Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results. Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists. In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal. Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments. Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs. Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era.

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DEGseq: an R package for identifying differentially expressed genes from RNA-seq data.

Likun Wang, Zhixing Feng, Xi Wang … (2010)

High-throughput RNA sequencing (RNA-seq) is rapidly emerging as a major quantitative transcriptome profiling platform. Here, we present DEGseq, an R package to identify differentially expressed genes or isoforms for RNA-seq data from different samples. In this package, we integrated three existing methods, and introduced two novel methods based on MA-plot to detect and visualize gene expression difference. The R package and a quick-start vignette is available at http://bioinfo.au.tsinghua.edu.cn/software/degseq

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KOBAS-i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis

Dechao Bu, Haitao Luo, Peipei Huo … (2021)

Gene set enrichment (GSE) analysis plays an essential role in extracting biological insight from genome-scale experiments. ORA (overrepresentation analysis), FCS (functional class scoring), and PT (pathway topology) approaches are three generations of GSE methods along the timeline of development. Previous versions of KOBAS provided services based on just the ORA method. Here we presented version 3.0 of KOBAS, which is named KOBAS-i (short for KOBAS intelligent version). It introduced a novel machine learning-based method we published earlier, CGPS, which incorporates seven FCS tools and two PT tools into a single ensemble score and intelligently prioritizes the relevant biological pathways. In addition, KOBAS has expanded the downstream exploratory visualization for selecting and understanding the enriched results. The tool constructs a novel view of cirFunMap, which presents different enriched terms and their correlations in a landscape. Finally, based on the previous version's framework, KOBAS increased the number of supported species from 1327 to 5944. For an easier local run, it also provides a prebuilt Docker image that requires no installation, as a supplementary to the source code version. KOBAS can be freely accessed at http://kobas.cbi.pku.edu.cn , and a mirror site is available at http://bioinfo.org/kobas . Graphical Abstract Framework of KOBAS.

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Author and article information

Contributors

Hui Zeng

Qiang Liu

Zigang Ge

Jianhao Lin

Journal

Journal ID (nlm-ta): J Orthop Translat

Journal ID (iso-abbrev): J Orthop Translat

Title: Journal of Orthopaedic Translation

Publisher: Chinese Speaking Orthopaedic Society

ISSN (Print): 2214-031X

ISSN (Electronic): 2214-0328

Publication date PMC-release: 05 July 2024

Publication date Collection: July 2024

Publication date (Electronic): 05 July 2024

Volume: 47

Pages: 235-248

Affiliations

[a ]Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China

[b ]Arthritis Institute, Peking University, Beijing, 100044, China

[c ]Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, 518036, China

[d ]Department of Biomedical Engineering, Institute of Future Technology, Peking University, Beijing, 100871, China

[e ]Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China

[f ]Department of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, 030001, China

[g ]Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, 230041, China

[h ]Institute of Medical Science, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China

[i ]Department of Orthopedics, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, China

Author notes

[* ]Corresponding author. Department of Orthopedics, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518035, China. zenghui_36@ 123456163.com

[** ]Corresponding author. Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China. liuqiang_pku@ 123456126.com

[*** ]Corresponding author. Department of Biomedical Engineering, Institute of Future Technology, Peking University, Beijing, 100871, China. gez@ 123456pku.edu.cn

[**** ]Corresponding author. Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China. linjianhao@ 123456pkuph.edu.cn

[1]

These authors contributed equally to this work.

Article

Publisher Item ID: S2214-031X(24)00031-7

DOI: 10.1016/j.jot.2024.03.006

PMC ID: 11332990

PubMed ID: 39161657

SO-VID: 9ca8e305-13fa-44d2-96b0-573db8d58a46

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 4 January 2024

Date revision received : 25 February 2024

Date accepted : 21 March 2024

Functionally improved mesenchymal stem cells via nanosecond pulsed electric fields for better treatment of osteoarthritis

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Abstract

Background

Methods

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Conclusions

The translational potential of this article

Graphical abstract

Related collections

Bacterial extracellular vesicles

Most cited references 44

Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

DEGseq: an R package for identifying differentially expressed genes from RNA-seq data.

KOBAS-i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis

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