Effects of Low Intensity Ultrasoundon Chondrogenesis of Bone Marrow Mesenchymal Stem Cells

INTRODUCTION Bone marrow mesenchymal stem cells (MSCs) are undifferentiated pluripotential cells capable of differentiating into many cell types, such as osteoblasts, chondrocytes, adipocytes, myocytes, and may be a suitable autogenous cell source for articular cartilage repair. In vitro experiments show markers of chondrogenesis, such as aggrecan and collagen type II, are expressed in MSCs cultures. Furthermore, in vivo experiments show stem cells implanted into surgically created osteochondral defects in rabbits are able to differentiate into chondrocytes and improve the quality of cartilaginous repair tissue. There are clinical advantages of using bone marrow-derived MSCs as donor cells in articular cartilage repair, but several limitations have been demonstrated in inducing chondrogenesis of MSC. Methods to stimulate proliferation and subsequent chondrogenic differentiation of MSCs are needed to further develop the use of cultured MSCs for articular defect repair. Several growth factors including TGF, IGF, BMPs are known to promote chondrogenesis or demonstrate chondrogenic effects both in vivo and in vitro in MSCs. In addition, three-dimentional culture system, such as pellet or alginate culture could facilitate the chondrogenic differentiation of MSCs. However, these factors are not sufficient for the induction of chondrogenesis efficiently and reproducibly. Chondrogenesis in cartilage development and repair and cartilage degeneration can be regulated by mechanical-load-induced physical factors such as tissue deformation, interstitial fluid flow and pressure, and electrical fields or streaming potentials. Recently, low intensity ultrasound (LIUS) has been shown to augment fracture healing and increase the mechanical strength of fracture callus in clinical studies and animal models. These observations suggest that the mechanical stimulation by LIUS could be one of the important factors in chondrogenic pathway in MSCs, even though the underlying mechanisms of LIUS action still remain unclear. However, to date, there have been no reports yet which demonstrate the chondrogenic effects of US on MSCs. The aim of this study was to examine the possible role of LIUS in chondrogenic differentiation of rabbit bone marrow MSCs.