SOX - 6,9 -Transfected Adipose Stem Cells to Treat Surgically-Induced Osteoarthritis in Goats

Abstract

The authors developed SOX-6, 9-transfected human adipose stem cells (^{SOX-6, 9}ASCs) to treat osteoarthritis (OA) and tested their effectiveness in arresting OA progression when injected intra-articularly (IA) in a surgically-induced OA caprine model. ^{SOX-6, 9}ASCs demonstrated similar in vitro chondrogenic potential, as determined by proteoglycan production, to ASCs treated with TGF-β₂ and BMP-7 (positive control). In contrast, the messenger RNA (mRNA) expressions of COL2A1 and aggrecan were 3.5-fold (p = 0.004) and 1.4-fold (p = 0.058) higher, respectively, in ^{SOX-6, 9}ASCs than in the positive control. In vivo tracking of injected ^{SOX-6, 9}ASCs in rats demonstrated that these cells disappear from the joint cavity within 2 weeks, suggesting paracrine mode of action. In a surgically-induced goat model of OA, IA ^{SOX-6, 9}ASCs at a dose of 0.6 × 10⁷ best preserved articular cartilage and produced significantly better macroscopic and microscopic scores than negative controls in femoral and tibial articular surfaces. In conclusion, SOX-6, 9-transfection led to in vitro chondrogenesis of ASCs comparable to that achieved by growth factor treatment. IA injection of ^{SOX-6, 9}ASCs in optimal dose reduced the progression of surgically-induced OA in goats. We suggest that ^{SOX-6, 9}ASCs offer a novel potential strategy to treat OA.

Impact Statement

We developed SOX-6, 9-transfected human adipose stem cells (^{SOX-6, 9}ASCs) to treat osteoarthritis (OA). SOX-6, 9-transfection led to in vitro chondrogenesis of adipose stem cells (ASCs) comparable to that achieved by growth factor treatment. Intra-articular injection of SOX-6, 9-transfected ASCs reduced the progression of surgically-induced OA in goats. In vivo tracking of transfected cell suggested paracrine mode of action. We think that SOX-6, 9-transfected ASC provides a novel potential strategy for the treatment of OA.