Hydrostatic Pressure Enhances Chondrogenic Differentiation of Human Multipotential Mesenchymal Cells in Alginate Disks

INTRODUCTION The poor intrinsic healing capacity of articular cartilage and the limited number of cells available for transplantation have engendered much interest in the development of an alternative source of chondrocytes for tissue engineering applications. One such cell population is multipotential mesenchymal cells (MMCs), which are readily obtained from bone marrow and may be induced to differentiate along a number of different lineages [1,3]. These cells are expandable in culture, and can be grown in sufficient numbers to populate tissue-engineered constructs. MMCs in pellet or micromass culture can be differentiated towards a chondrogenic phenotype with the application of growth factors, such as those from the TGF superfamily, including TGF-β1 [2] and -β3 [3], and BMP-2 [4]. More recently it has been shown that these cells can differentiate in situ in scaffolds such as fibrin and alginate hydrogels [3,5,6] as well as in PGA felts [7] and PLA/alginate amalgams [8]. While the process of chemically induced differentiation is well understood, the role of mechanical forces in the differentiation process has yet to be fully characterized. Studies of embryonic development in chick eggs have long documented the role of physical forces in initiating and maintaining joint development [9]. More recently, studies using limb bud cells have shown that dynamic loading may encourage the chondrogenic differentiation of a greater number of these cells than would otherwise occur [10]. Moreover, recent theoretical studies have suggested a role for physical forces (such as hydrostatic pressure) in the growth of developing limbs [11]. In this study, we examined the role of one mechanical signal, dynamic hydrostatic pressurization, in the chondrogenic differentiation of human MMCs in an alginate disk culture system.