Cartilage organoids for cartilage development and cartilage-associated disease modeling

Weiping Lin; Min Wang; Liangliang Xu; Micky Tortorella; Gang Li

doi:10.3389/fcell.2023.1125405

Cartilage organoids for cartilage development and cartilage-associated disease modeling

Front Cell Dev Biol. 2023 Jan 30:11:1125405. doi: 10.3389/fcell.2023.1125405. eCollection 2023.

Authors

Weiping Lin^{1

2}, Min Wang³, Liangliang Xu⁴, Micky Tortorella^{1

5}, Gang Li^{6

7

8}

Affiliations

¹ Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong SAR, China.
² The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
³ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
⁴ The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
⁵ Drug Discovery Pipeline at the Guangzhou Institutes for Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
⁶ Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
⁷ Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
⁸ Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.

Abstract

Cartilage organoids have emerged as powerful modelling technology for recapitulation of joint embryonic events, and cartilage regeneration, as well as pathophysiology of cartilage-associated diseases. Recent breakthroughs have uncovered "mini-joint" models comprising of multicellular components and extracellular matrices of joint cartilage for development of novel disease-modifying strategies for personalized therapeutics of cartilage-associated diseases. Here, we hypothesized that LGR5-expressing embryonic joint chondroprogenitor cells are ideal stem cells for the generation of cartilage organoids as "mini-joints" ex vivo "in a dish" for embryonic joint development, cartilage repair, and cartilage-associated disease modelling as essential research models of drug screening for further personalized regenerative therapy. The pilot research data suggested that LGR5-GFP-expressing embryonic joint progenitor cells are promising for generation of cartilage organoids through gel embedding method, which may exert various preclinical and clinical applications for realization of personalized regenerative therapy in the future.

Keywords: LGR5; cartilage organoids; mini-joint; regenerative therapy; stem cells.