ANTI-Fibrotic and ANTI-Hypertrophic Effect Of Adipose Mesenchymal Stromal CELLS On Osteoarthritic Chondrocytes

Marie Maumus¹, C. Manferdini², Karine Toupet¹, A. Piacentini², A. Gabusi², A. Facchini², G. Lisignoli², Christian Jorgensen³ and Daniele Noel⁴, ¹Université Montpellier1, INSERM U844, Montpellier, France, ²Laboratorio di Immunoreumatologia e Rigenerazione tissutale, IOR BOLOGNA, BOLOGNA, Italy, ³Department of therapy & Immuno-Rhumatology, Inserm U844, CHU saint-Eloi, Université Montpellier 1, CHU Lapeyronie, Montpellier, France, ⁴Inserm U844, UM1, Montpellier, France

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: adipose tissue, chondrocytes, osteoarthritis and stem cells

Session Information

Title: Biology and Pathology of Bone and Joint (Cartilage and Osteoarthritis)

Session Type: Abstract Submissions (ACR)

Background/Purpose: Mesenchymal stem cells (MSC) isolated from bone marrow (MSC) or adipose (ASC) tissues secrete a large amount of trophic factors. The possibility that these cells, through their paracrine potential, may influence the course of chronic degenerative disorders and prevent cartilage degradation is promising for the treatment of osteoarthritis (OA). Indeed, the aim of our work was to evaluate the effects of these cells on OA chondrocyte phenotype.

Methods: OA ASC were isolated from intra-articular (Hoffa-ASC) or hip (hip ASC) subcutaneous adipose tissue and healthy ASC from subcutaneous abdominal depot (abdo-ASC). BM-MSC and chondrocytes were obtained from OA donors. ASC or MSC were co-incubated with chondrocytes cultured in monolayer during 7 days using cell culture inserts. Expression of markers specific for mature and hypertrophic chondrocytes or fibroblasts was quantified by RT-qPCR or ELISA. Isotypic or anti-HGF antibodies (100ng/ml) were added during the coculture.

Results: After 7 days of ASC or MSC co-cultures with chondrocytes, a stable expression of the markers specific for mature chondrocytes (Col IIB, Agg, link, Sox9) was observed, while expression of hypertrophic (MMP13, AP) and fibrotic (Col I and III) markers was significantly decreased. Compared to abdo-ASCs, Hoffa- and Hip-ASC reduced less efficiently the expression of hypertrophic/fibrotic markers and some markers of mature chondrocytes were decreased with Hip-ASC. Finally, factors known to be involved in fibrosis and matrix remodeling (TIMP-1 and -2, MMP-1 and -9, IL1-RA) were not changed. On the contrary, HGF secretion was induced and addition of neutralizing anti-HGF antibody reversed the anti-fibrotic effect of ASC whereas the hypertrophic markers were not modulated.

Conclusion:

ASC from abdominal subcutaneous fat and MSC were the most efficient to reduce hypertrophy and dedifferentiation of articular chondrocytes. This effect was at least partly due to the induction of HGF secretion confirming the interest of using ASC in therapies of osteo-articular diseases.

Disclosure:

M. Maumus,
None;

C. Manferdini,
None;

K. Toupet,
None;

A. Piacentini,
None;

A. Gabusi,
None;

A. Facchini,
None;

G. Lisignoli,
None;

C. Jorgensen,
None;

D. Noel,
None.

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-fibrotic-and-anti-hypertrophic-effect-of-adipose-mesenchymal-stromal-cells-on-osteoarthritic-chondrocytes/