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Theranostics 2024; 14(2):879-891. doi:10.7150/thno.87843 This issue Cite

Research Paper

Initial IL-10 production dominates the therapy of mesenchymal stem cell scaffold in spinal cord injury

Lijun Yang^1,2,3*, Jian Cao^4*, Yiwen Du^1,2,3, Xunqi Zhang⁴, Wenxiang Hong^1,2,3, Bowen Peng^1,2,3, Jiahe Wu⁴, Qinjie Weng^1,2,3,6, Jiajia Wang^1,2,3✉, Jianqing Gao^3,4,5,6,7✉

1. Center for Drug Safety Evaluation and Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
2. Nanhu Brain-computer Interface Institute, Hangzhou, 311100, China.
3. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
4. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
5. Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China.
6. Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
7. National Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
*These authors contributed equally to this work: Lijun Yang, Jian Cao.

✉ Corresponding authors: Jianqing Gao, Email: gaojianqingedu.cn; Jiajia Wang, Email: wangjiajia3301edu.cn.

Abstract

Rationale: Spinal cord injury (SCI) is an acute damage to the central nervous system that results in severe morbidity and permanent disability. Locally implanted scaffold systems with immobilized mesenchymal stem cells (MSCs) have been widely proven to promote locomotor function recovery in SCI rats; however, the underlying mechanism remains elusive.

Methods and Results: In this study, we constructed a hyaluronic acid scaffold system (HA-MSC) to accelerate the adhesive growth of human MSCs and prolong their survival time in SCI rat lesions. MSCs regulate local immune responses by upregulating the expression of anti-inflammatory cytokines. Interestingly, the dramatically increased, but transient expression of interleukin 10 (IL-10) is found to be secreted by MSCs in the first week. Blocking the function of the initially produced IL-10 by the antibody completely abolished the neurological and behavioral recovery of SCI rats, indicating a core role of IL-10 in SCI therapy with HA-MSC implantation. Transcriptome analyses indicated that IL-10 selectively promotes the migration and cytokine secretion-associated programs of MSCs, which in turn helps MSCs exert their anti-inflammatory therapeutic effects.

Conclusion: Our findings highlight a novel role of IL-10 in regulating MSC migration and cytokine secretion-associated programs, and determine the vital role of IL-10 in the domination of MSC treatment for spinal cord repair.

Keywords: mesenchymal stem cells, IL-10, spinal cord injury, cell migration, cytokines secretion

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