Exosomes derived from umbilical cord mesenchymal stem cells protect cartilage and regulate the polarization of macrophages in osteoarthritis

Pengdong Li; Shuang Lv; Wenyue Jiang; Lihui Si; Baojian Liao; Guifang Zhao; Ziran Xu; Lina Wang; Jia Zhang; Haitao Wu; Qian Peng; Zhaohui Li; Ling Qi; Guangfan Chi; Yulin Li

doi:10.21037/atm-22-3912

Exosomes derived from umbilical cord mesenchymal stem cells protect cartilage and regulate the polarization of macrophages in osteoarthritis

Ann Transl Med. 2022 Sep;10(18):976. doi: 10.21037/atm-22-3912.

Authors

Pengdong Li¹, Shuang Lv¹, Wenyue Jiang², Lihui Si³, Baojian Liao², Guifang Zhao², Ziran Xu¹, Lina Wang¹, Jia Zhang², Haitao Wu¹, Qian Peng², Zhaohui Li², Ling Qi², Guangfan Chi¹, Yulin Li¹

Affiliations

¹ The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, Changchun, China.
² The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
³ Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, China.

Abstract

Background: Osteoarthritis (OA) is one of the most common joint diseases and a major global public health concern. Mesenchymal stem cells (MSCs) have been widely used for the treatment of OA owing to their paracrine secretion of trophic factors, a phenomenon in which exosomes may play a major role. Here, we investigate the potential of exosomes from human umbilical cord-derived MSCs (hUC-MSCs-Exos) in alleviating OA.

Methods: The hUC-MSCs-Exos were harvested from hUC-MSC-conditioned medium using ultracentrifugation. Rats with surgically-induced OA were intra-articularly injected with hUC-MSCs-Exos. The effect of hUC-MSCs-Exos in repairing osteoarticular cartilage was assessed using hematoxylin and eosin (HE) staining, safranin-O and fast green staining and immunohistochemistry. The in vitro experiments were further carried out to verify the therapeutic effect. The effects of hUC-MSCs-Exos on the proliferation and migration of human chondrocytes were evaluated using the cell counting kit-8, EdU-555 cell proliferation kit, and transwell assays. Annexin V-FITC/PI staining were used to evaluate the effect of exosomes on chondrocyte apoptosis. An in vitro model of human articular chondrocytes treated with interleukin 1 beta (IL-1β) was used to evaluate the effects of exosomes, analyses involved using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting. The role of hUC-MSCs-Exos in macrophage polarization was examined in the monocyte cell line, Tohoku Hospital Pediatrics-1 (THP-1) by qRT-PCR and immunofluorescence.

Results: The results showed that hUC-MSCs-Exos prevented severe damage to the knee articular cartilage in the rat OA model. We confirmed the high efficacy of hUC-MSCs-Exos in promoting chondrocyte proliferation and migration and inhibiting chondrocyte apoptosis. Additionally, hUC-MSCs-Exos could reverse IL-1β-induced injury of chondrocytes and regulate the polarization of macrophages in vitro.

Conclusions: There is potential for hUC-MSCs-Exos to be used as a treatment strategy for OA.

Keywords: Human umbilical cord-derived-mesenchymal stem cell (hUC-MSCs); chondrocyte; exosome; macrophage; osteoarthritis (OA).