Cell-based therapy in the repair of osteochondral defects: a novel use for adipose tissue.
ABSTRACT Mesenchymal stem cells are currently procured from periosteum and bone marrow. The procurement of stem cells from these sources is tedious and gives a low yield of cells. This study was aimed at circumventing these problems and allowing for a method that would be more acceptable in the clinical setting. Tissue for transplantation was harvested from a single New Zealand White rabbit. Cells were more readily obtained from adipose tissue than from bone marrow or periosteum. The present method also provided a better yield of cells through culture. In vitro studies were performed to assess the differentiation potential of these cells. Successful in vitro transformation into alternative mesenchymal cell lines including cardiomyocytes revealed these cells to have wide differentiation potential. Further characterization morphologically, immunohistochemically, and via gene transfection showed features consistent with mesenchymal stem cells. Cultured cells were then transplanted into defects created in the left medial femoral condyle. The femora were harvested at various intervals and the repair tissue was assessed. Gross osteochondral defect reconstitution and histological grading was superior to periosteum-derived stem cell repair and repair by native mechanisms. Biomechanically, the repair tissue approximated intact cartilage and was superior to osteochondral autografts and repair by innate mechanisms.
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ABSTRACT: Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Maturation involves gross morphological changes that occur through a process of synchronised growth and resorption of cartilage and generally ends at sexual maturity. The inability to induce maturation in biomaterial constructs designed for cartilage repair has been cited as a major cause for their failure in producing persistent cell-based repair of joint lesions. The combination of growth factors FGF2 and TGFβ1 induces accelerated articular cartilage maturation in vitro such that many molecular and morphological characteristics of tissue maturation are observable. We hypothesised that experimental growth factor-induced maturation of immature cartilage would result in a biophysical and biochemical composition consistent with a mature phenotype. Using native immature and mature cartilage as reference, we observed that growth factor-treated immature cartilages displayed increased nano-compressive stiffness, decreased surface adhesion, decreased water content, increased collagen content and smoother surfaces, correlating with a convergence to the mature cartilage phenotype. Furthermore, increased gene expression of surface structural protein collagen type I in growth factor-treated explants compared to reference cartilages demonstrates that they are still in the dynamic phase of the postnatal developmental transition. These data provide a basis for understanding the regulation of postnatal maturation of articular cartilage and the application of growth factor-induced maturation in vitro and in vivo in order to repair and regenerate cartilage defects.Biomaterials 11/2012; 34(5). DOI:10.1016/j.biomaterials.2012.09.076 · 8.31 Impact Factor
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ABSTRACT: Adipose tissue is an ideal tissue to use as an autologous substitute with which to approach tissue deficiency. Clinically, the use of fat grafts and adipose-derived stem cells has dramatically increased worldwide for reconstructive and aesthetic purposes. Human adipose tissue contains a population of pluripotent stem cells capable of differentiating along multiple mesenchymal cell lineages. Adipose tissue is an abundant, expendable, and easily obtained tissue that may prove to be an ideal source of autologous stem cells for regenerating tissues. The recent identification and characterization of multilineage cells from human adipose tissue has been met with a great deal of excitement by the field of tissue engineering. The authors' laboratory has characterized a population of cells obtained from human adipose tissue that have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, and neuron-like cells in vitro. This article summarizes the basic study of the adipose tissue as a multipotential stem cell source of tissue engineering techniques that are currently being developed to solve common aesthetic problems.Journal of the Korean Medical Association 01/2012; 55(8):757. DOI:10.5124/jkma.2012.55.8.757 · 0.18 Impact Factor
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ABSTRACT: Stem cells are unique cells exhibiting self-renewing properties and the potential to differentiate into multiple specialised cell types. Totipotent or pluripotent stem cells are generally abundant in embryonic or fetal tissues, but the use of discarded embryos as sources of these cells raises challenging ethical problems. Adult stem cells can also differentiate into a wide variety of cell types. In particular, adult adipose tissue contains a pool of abundant and accessible multipotent stem cells, designated as adipose-derived stem cells (ASCs), that are able to replicate as undifferentiated cells, to develop as mature adipocytes and to differentiate into multiple other cell types along the mesenchymal lineage, including chondrocytes, myocytes and osteocytes, and also into cells of endodermal and neuroectodermal origin, including beta-cells and neurons, respectively. An impairment in the differentiation potential and biological functions of ASCs may contribute to the development of obesity and related comorbidities. In this review, we summarise different aspects of the ASCs with special reference to the isolation and characterisation of these cell populations, their relation to the biochemical features of the adipose tissue depot of origin and to the metabolic characteristics of the donor subject and discuss some prospective therapeutic applications.Expert Reviews in Molecular Medicine 12/2012; 14:e19. DOI:10.1017/erm.2012.13 · 5.91 Impact Factor