Infrapatellar fat pad adipose-derived stem cells co-cultured with articular chondrocytes from osteoarthritis patients exhibit increased chondrogenic gene expression

Cell Communication and Signaling

Kendrick To¹  Karim Fekir²  Roger A. Brooks²  Christopher C. H. Mak³  Wasim S. Khan⁴ 

[1] Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1PD, Cambridge, UK;Division of Trauma and Orthopaedic Surgery, Department of Surgery, Addenbrooke’s Hospital, University of Cambridge, Hills Road, CB2 0QQ, Cambridge, UK;School of Clinical Medicine, Hills Road, CB2 0QQ, Cambridge, UK;Versus Arthritis Tissue Engineering and Regenerative Therapies Centre, Division of Trauma and Orthopaedic Surgery, Department of Surgery, Addenbrooke’s Hospital, University of Cambridge, Hills Road, CB2 0QQ, Cambridge, UK;

关键词: Mesenchymal stromal cells;    Co-culture;    Chondrogenesis;    Cartilage;    Cell-based therapy;    Regenerative medicine;    Osteoarthritis;   

DOI  :  10.1186/s12964-021-00815-x

来源: Springer

【 摘 要 】

AimThe variable results in clinical trials of adipose tissue-derived stem cells (ASCs) for chondral defects may be due to the different ex vivo culture conditions of the ASCs which are implanted to treat the lesions. We sought to determine the optimal in vitro chondrocyte co-culture condition that promotes infrapatellar fat pad-derived (IFPD) ASC chondrogenic gene expression in a novel co-culture combination.MethodsIn our study, we utilized an in vitro autologous co-culture of IFPD ASCs and articular chondrocytes derived from Kellgren–Lawrence Grade III/IV osteoarthritic human knee joints at ASC-to-chondrocyte seeding log ratios of 1:1, 10:1, and 100:1. Gene expression following in vitro co-culture was quantified by RT-qPCR with a panel comprising COL1A1, COL2A1, COL10A1, L-SOX5, SOX6, SOX9, ACAN, HSPG2, and COMP for chondrogenic gene expression.ResultsThe chondrogenic gene expression profiles from co-cultures were greater than would be expected from an expression profile modeled from chondrocyte and ASC-only monocultures. Additionally, chondrogenic gene expression decreased with increasing ASC-to-chondrocyte seeding ratios.ConclusionsThese findings provide insight into the mechanisms underlying clinical ASC therapies and signifies that IFPD ASCs pre-conditioned by chondrocyte co-culture may have improved chondrogenic potential for cartilage repair. This model can help further understand IFPD ASCs in chondral and osteochondral repair and the chondrogenic pathways involved.5w6sq_raPc9bkGgSr2Nbk9Video Abstract

【 授权许可】

CC BY