Enhanced osteoarthritis therapy by nanoengineered mesenchymal stem cells using biomimetic CuS nanoparticles loaded with plasmid DNA encoding TGF-β1

Yu Cai; Cuixi Wu; Qianhua Ou; Muhui Zeng; Song Xue; Jieli Chen; Yao Lu; Changhai Ding

doi:10.1016/j.bioactmat.2022.04.021

Enhanced osteoarthritis therapy by nanoengineered mesenchymal stem cells using biomimetic CuS nanoparticles loaded with plasmid DNA encoding TGF-β1

Bioact Mater. 2022 May 2:19:444-457. doi: 10.1016/j.bioactmat.2022.04.021. eCollection 2023 Jan.

Authors

Yu Cai^{1

2}, Cuixi Wu¹, Qianhua Ou¹, Muhui Zeng^{1

2}, Song Xue^{1

3}, Jieli Chen¹, Yao Lu^{1

2

4}, Changhai Ding^{1

5

6}

Affiliations

¹ Clinical Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China.
² Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China.
³ Department of Rheumatology and Immunology, Arthritis Research Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China.
⁴ Guangdong Key Lab of Orthopedic Technology and Implant, Guangzhou, Guangdong, 510010, China.
⁵ Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Southern Medical University, Guangzhou, Guangdong, 510630, China.
⁶ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, 7000, Australia.

Abstract

Mesenchymal stem cells (MSCs) therapy shows the potential benefits to relieve clinical symptoms of osteoarthritis (OA), but it is uncertain if it can repair articular cartilage lesions - the main pathology of OA. Here, we prepared biomimetic cupper sulfide@phosphatidylcholine (CuS@PC) nanoparticles (NPs) loaded with plasmid DNA (pDNA) encoding transforming growth factor-beta 1 (TGF-β1) to engineer MSCs for enhanced OA therapy via cartilage regeneration. We found that the NPs not only promoted cell proliferation and migration, but also presented a higher pDNA transfection efficiency relative to commercial transfection reagent lipofectamine 3000. The resultant CuS/TGF-β1@PC NP-engineered MSCs (termed CTP-MSCs) were better than pure MSCs in terms of chondrogenic gene expression, glycosaminoglycan deposition and type II collagen formation, favoring cartilage repair. Further, CTP-MSCs inhibited extracellular matrix degradation in interleukin-1β-induced chondrocytes. Consequently, intraarticular administration of CTP-MSCs significantly enhanced the repair of damaged cartilage, whereas pure MSCs exhibited very limited effects on cartilage regeneration in destabilization of the medial meniscus (DMM) surgical instability mice. Hence, this work provides a new strategy to overcome the limitation of current stem cell therapy in OA treatment through developing more effective nanoengineered MSCs.

Keywords: Cartilage regeneration; Cupper sulfide nanoparticles; Gene delivery; Osteoarthritis; Stem cell therapy.