Chondrogenesis of bone marrow-derived mesenchymal stem cells in alginate hydrogels under various culture conditions - a pilot study
Erali, Richard A.
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Osteoarthritis (OA) is a major concern among healthcare providers as its increasing prevalence has not shaped sufficiently adequate therapies to slow or reverse the onset of OA. Further, traumatic injury to joints in the young population can lead to early arthritic changes characteristic of the elderly population. The spontaneous regeneration of injured articular cartilage (AC) is virtually non-existent and current treatments focus on pain management and reestablishing patient mobility. No current treatments restore the AC surface to its pre-injured state, biomechanically or biochemically. Cartilage tissue engineering has expanded the potential toolbox of treatment options. Bone marrow derived mesenchymal stem cells (BMSCs) and chondrocytes are the most common cell sources for AC tissue engineering. Yet, few studies have investigated the use of a co-culture model, combing both cell sources into one hydrogel. In this study, swine BMSCs and chondrocytes were co-cultured (1:1 ratio) in a 2% sodium alginate hydrogel and implanted subcutaneously into the backs of old nude mice for 6 weeks. For comparison, two other groups were designed to study the effectiveness of this co-culture model: BMSCs only and chondrocytes only. A previous study with BMSCs grown in chondrocyte conditioned media was also evaluated with the co-culture groups. All groups (n=4) spent 2 weeks in vitro under the influence of chondrogenic differentiation media prior to implantation. Histological examination showed extracellular matrix formation in all gels. The BMSCs only group showed the continuous formation of matrix, while the co-culture group showed isolated pericellular matrix. The conditioned BMSCs showed the most continuous matrix formation. Not surprisingly, glycosaminoglycan (GAG) and hydroxyproline assays reported the chondrocyte gel group as the most biochemically active. The co-culture group produced the lowest amounts of GAG and hydroxyproline. This study shows that BMSCs and chondrocytes co-cultured in a 1:1 ratio does not provide a significant advantage in cartilage matrix production in comparison with BMSCs and chondrocytes cultured separately. Further studies on the proper ratio and in vitro conditions will be the next step in defining a model for co-culture of BMSCs and chondrocytes.
Thesis (M.A.)--Boston University