Journal
CELL COMMUNICATION AND SIGNALING
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12964-021-00815-x
Keywords
Mesenchymal stromal cells; Co-culture; Chondrogenesis; Cartilage; Cell-based therapy; Regenerative medicine; Osteoarthritis
Categories
Funding
- Royal College of Surgeons of England
- Versus Arthritis through Versus Arthritis Tissue Engineering & Re-generative Therapies Centre [21156]
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The aim of this study was to determine the optimal in vitro chondrocyte co-culture condition that promotes infrapatellar fat pad-derived (IFPD) ASC chondrogenic gene expression. The results showed that co-culture increased chondrogenic gene expression, and the expression level decreased with increasing ASC-to-chondrocyte seeding ratios. These findings provide important insights into the mechanisms of clinical ASC therapies.
Aim: The 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. Methods: In 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. Results: The 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. Conclusions: These 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.
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