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


Type
Article
Change log
Authors
Mak, Christopher CH 
Fekir, Karim 
Brooks, Roger A 
Khan, Wasim S 
Abstract

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. Video Abstract.

Description
Keywords
Cartilage, Cell-based therapy, Chondrogenesis, Co-culture, Mesenchymal stromal cells, Osteoarthritis, Regenerative medicine, Adipose Tissue, Cell Differentiation, Cells, Cultured, Chondrocytes, Coculture Techniques, Gene Expression, Humans, Knee Joint, Osteoarthritis, Stem Cells
Journal Title
Cell Commun Signal
Conference Name
Journal ISSN
1478-811X
1478-811X
Volume Title
20
Publisher
Springer Science and Business Media LLC
Sponsorship
ARTHRITIS RESEARCH UK (21156)