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

Jianjing Lin; Kejia Li; Zhen Yang; Fuyang Cao; Liang Gao; Tong Ning; Dan Xing; Hui Zeng; Qiang Liu; Zigang Ge; Jianhao Lin

Journal of Orthopaedic Translation (Jul 2024)

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

Jianjing Lin,
Kejia Li,
Zhen Yang,
Fuyang Cao,
Liang Gao,
Tong Ning,
Dan Xing,
Hui Zeng,
Qiang Liu,
Zigang Ge,
Jianhao Lin

Affiliations

Jianjing Lin: Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China; Arthritis Institute, Peking University, Beijing, 100044, China; Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, 518036, China
Kejia Li: Department of Biomedical Engineering, Institute of Future Technology, Peking University, Beijing, 100871, China; 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
Zhen Yang: Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China; Arthritis Institute, Peking University, Beijing, 100044, China
Fuyang Cao: Department of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, 030001, China
Liang Gao: Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, 230041, China
Tong Ning: Institute of Medical Science, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China
Dan Xing: Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China; Arthritis Institute, Peking University, Beijing, 100044, China
Hui Zeng: Department of Orthopedics, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, China; Corresponding author. Department of Orthopedics, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518035, China.
Qiang Liu: Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China; Arthritis Institute, Peking University, Beijing, 100044, China; Corresponding author. Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China.
Zigang Ge: Department of Biomedical Engineering, Institute of Future Technology, Peking University, Beijing, 100871, China; Corresponding author. Department of Biomedical Engineering, Institute of Future Technology, Peking University, Beijing, 100871, China.
Jianhao Lin: Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China; Arthritis Institute, Peking University, Beijing, 100044, China; Corresponding author. Arthritis Clinical and Research Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China.

Journal volume & issue: Vol. 47
pp. 235 – 248

Abstract

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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.

Published in Journal of Orthopaedic Translation

ISSN: 2214-031X (Print); 2214-0328 (Online)
Publisher: Elsevier
Country of publisher: Hong Kong
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the musculoskeletal system
Website: http://www.journals.elsevier.com/journal-of-orthopaedic-translation/

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