The role of stem cells in osteoarthritis: An experimental study in rabbits

Abstract

Introduction: Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair.

Methods: In this study, we used scaffold-free mesenchymal stem cells (MSCs) obtained from bone marrow in an experimental animal model of OA by direct intra-articular injection. MSCs were isolated from 2.8 kg white New Zealand rabbits. There were ten in the study group and ten in the control group. OA was induced by unilateral transection of the anterior cruciate ligament of the knee joint. At 12 weeks post-operatively, a single dose of 1 million cells suspended in 1 ml of medium was delivered to the injured knee by direct intra-articular injection. The control group received 1 ml of medium without cells. The knees were examined at 16 and 20 weeks following surgery. Repair was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining.

Results: Radiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving MSCs showed a lower degree of cartilage degeneration, osteophyte formation, and subchondral sclerosis than the control group at 20 weeks post-operatively. The quality of cartilage was significantly better in the cell-treated group compared with the control group after 20 weeks.

Conclusions: Bone marrow-derived MSCs could be promising cell sources for the treatment of OA. Neither stem cell culture nor scaffolds are absolutely necessary for a favourable outcome. Cite this article: Bone Joint Res 2014;3:32-7.

Keywords: MSC; Mesenchymal stem cells; OA; Osteoarthritis; Rabbit model; Repair.

Figs. 1a - 1d

Figures 1a and 1b – gross photographs of femoral condyles in the mesenchymal stem cell (MSC)-treated group a) at 16 weeks post-operatively, showing a reduction in lesion severity and b) at 20 weeks post-operatively, showing further reduction in lesion severity. Figures 1c and 1d – gross photographs of femoral condyles in the control group at c) 16 and d) 20 weeks post-operatively, showing characteristics of osteoarthritis (OA) becoming more evident between time-points.

Figs. 1a - 1d

Figures 1a and 1b – gross photographs of femoral condyles in the mesenchymal stem cell (MSC)-treated group a) at 16 weeks post-operatively, showing a reduction in lesion severity and b) at 20 weeks post-operatively, showing further reduction in lesion severity. Figures 1c and 1d – gross photographs of femoral condyles in the control group at c) 16 and d) 20 weeks post-operatively, showing characteristics of osteoarthritis (OA) becoming more evident between time-points.

Figs. 1a - 1d

Figures 1a and 1b – gross photographs of femoral condyles in the mesenchymal stem cell (MSC)-treated group a) at 16 weeks post-operatively, showing a reduction in lesion severity and b) at 20 weeks post-operatively, showing further reduction in lesion severity. Figures 1c and 1d – gross photographs of femoral condyles in the control group at c) 16 and d) 20 weeks post-operatively, showing characteristics of osteoarthritis (OA) becoming more evident between time-points.

Figs. 1a - 1d

Figures 1a and 1b – gross photographs of femoral condyles in the mesenchymal stem cell (MSC)-treated group a) at 16 weeks post-operatively, showing a reduction in lesion severity and b) at 20 weeks post-operatively, showing further reduction in lesion severity. Figures 1c and 1d – gross photographs of femoral condyles in the control group at c) 16 and d) 20 weeks post-operatively, showing characteristics of osteoarthritis (OA) becoming more evident between time-points.

Figs. 2a - 2d

Figures 2a and 2b – histological images of articular cartilage in the mesenchymal stem cell (MSC)-treated group a) at 16 weeks and b) at 20 weeks post-operatively, showing appropriate thickness, normal distribution of the cells and consistent staining of the cartilage, with the surface layer showing very mild irregularity (haematoxylin and eosin, ×40). Figures 2c and 2d – histological images of articular cartilage in the control group c) at 16 weeks and d) at 20 weeks post-operatively, showing structural disorganisation and severe hypocellularity of chondrocytes.

Figs. 2a - 2d

Figures 2a and 2b – histological images of articular cartilage in the mesenchymal stem cell (MSC)-treated group a) at 16 weeks and b) at 20 weeks post-operatively, showing appropriate thickness, normal distribution of the cells and consistent staining of the cartilage, with the surface layer showing very mild irregularity (haematoxylin and eosin, ×40). Figures 2c and 2d – histological images of articular cartilage in the control group c) at 16 weeks and d) at 20 weeks post-operatively, showing structural disorganisation and severe hypocellularity of chondrocytes.

Figs. 2a - 2d

Figures 2a and 2b – histological images of articular cartilage in the mesenchymal stem cell (MSC)-treated group a) at 16 weeks and b) at 20 weeks post-operatively, showing appropriate thickness, normal distribution of the cells and consistent staining of the cartilage, with the surface layer showing very mild irregularity (haematoxylin and eosin, ×40). Figures 2c and 2d – histological images of articular cartilage in the control group c) at 16 weeks and d) at 20 weeks post-operatively, showing structural disorganisation and severe hypocellularity of chondrocytes.

Figs. 2a - 2d

Figures 2a and 2b – histological images of articular cartilage in the mesenchymal stem cell (MSC)-treated group a) at 16 weeks and b) at 20 weeks post-operatively, showing appropriate thickness, normal distribution of the cells and consistent staining of the cartilage, with the surface layer showing very mild irregularity (haematoxylin and eosin, ×40). Figures 2c and 2d – histological images of articular cartilage in the control group c) at 16 weeks and d) at 20 weeks post-operatively, showing structural disorganisation and severe hypocellularity of chondrocytes.

Figs. 3a - 3b

Figure 3a – anteroposterior (AP) radiographs at 16 weeks post-operatively in the mesenchymal stem cell (MSC)-treated group (left) and the control group (right). Figure 3b – AP radiographs at 20 weeks post-operatively in the MSC-treated group (left) and the control group (right). Radiological evaluation at both time-points shows less severe radiological signs of osteoarthritis (OA) (including osteophyte formation, subchondral bone sclerosis and articular surface irregularity) in the MSC group compared with the controls.

Figs. 3a - 3b

Figure 3a – anteroposterior (AP) radiographs at 16 weeks post-operatively in the mesenchymal stem cell (MSC)-treated group (left) and the control group (right). Figure 3b – AP radiographs at 20 weeks post-operatively in the MSC-treated group (left) and the control group (right). Radiological evaluation at both time-points shows less severe radiological signs of osteoarthritis (OA) (including osteophyte formation, subchondral bone sclerosis and articular surface irregularity) in the MSC group compared with the controls.