Cell-Based Therapy in the Repair of Osteochondral Defects: A Novel Use for Adipose Tissue

Department of Orthopedics, National University Hospital, National University of Singapore, Singapore.
Tissue Engineering (Impact Factor: 4.25). 09/2003; 9(4):733-44. DOI: 10.1089/107632703768247412
Source: PubMed

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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    • "In the patent by Yang et al.,21 decellularized omentum was proposed to be co-cultured with human kidney derived cells, urothelial cells, or endothelial cells in a tubular omentum matrix. However, adipose tissue is also a rich source of stem cells, the so-called adipose-derived stem cells, which have the capacity to differentiate along the adipogenic,55 chondrogenic, 56 myogenic,57 osteogenic,58 neurogenic,59 endothelial,60–63 and smooth muscle64 lineages. In our opinion, this kind of cells could be the most suitable ones for recellularization process. "
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    ABSTRACT: Homologous tissues, such as adipose tissue, may be an interesting source of acellular scaffolds, maintaining a complex physiological three-dimensional (3D) structure, to be recellularized with autologous cells. The aim of the present work is to evaluate the possibility of obtaining homologous acellular scaffolds from decellularization of the omentum, which is known to have a complex vascular network. Adult rat and human omenta were treated with an adapted decellularization protocol involving mechanical rupture (freeze-thaw cycles), enzymatic digestion (trypsin, lipase, deoxyribonuclease, ribonuclease) and lipid extraction (2-propanol). Histological staining confirmed the effectiveness of decellularization, resulting in cell-free scaffolds with no residual cells in the matrix. The complex 3D networks of collagen (azan-Mallory), elastic fibers (Van Gieson), reticular fibers and glycosaminoglycans (PAS) were maintained, whereas Oil Red and Sudan stains showed the loss of lipids in the decellularized tissue. The vascular structures in the tissue were still visible, with preservation of collagen and elastic wall components and loss of endothelial (anti-CD31 and -CD34 immunohistochemistry) and smooth muscle (anti-alpha smooth muscle actin) cells. Fat-rich and well vascularized omental tissue may be decellularized to obtain complex 3D scaffolds preserving tissue architecture potentially suitable for recellularization. Further analyses are necessary to verify the possibility of recolonization of the scaffold by adipose-derived stem cells in vitro and then in vivo after re-implantation, as already known for homologus implants in regenerative processes.
    European journal of histochemistry: EJH 01/2013; 57(1):e4. DOI:10.4081/ejh.2013.e4 · 2.04 Impact Factor
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    • "Above a threshold defect diameter of 3e6 mm, cartilage lesions rarely heal spontaneously leading to progressive cartilage degeneration [3] [4]. This latter impasse has been resolved to some extent through cell transplantation of culture expanded, autologous articular chondrocytes or mesenchymal stem cell populations into chondral defects [5] [6] [7] [8]. Further complications arise as transplanted cells initially adopt an immature cartilage phenotype that appears to be subject to phenotypic instability [9], resulting in the inappropriate production of fibrocartilage or calcified tissue, both of which are to varying degrees deleterious to joint function [10] [11]. "
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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 · 8.56 Impact Factor
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    • "Las Células Madres son precursoras de las células que existen en el cuerpo humano, cumpliendo un rol fundamental en el desarrollo embrionario (Caplan, 1991; Meyer & Wiesmann, 2006), y en el potencial regenerativo de los tejidos (Tokalov et al., 2007). Una vez diferenciados los tejidos su presencia se hace más escasa, no obstante lo cual numerosos estudios han reportado su aislamiento en tejidos diferenciados, tanto en médula ósea (Friedenstein et al., 1987; Javason et al., 2001; Rhodes et al., 2004; Tropel et al., 2004), como en otros tejidos (Nathan et al., 2003; de Ugarte et al., 2003; Nöth et al., 2002; Fickert et al., 2003; Baksh et al., 2004; Jo et al., 2007; Dualibi et al., 2008; Yao et al., 2008) habiendo sido también descritas en cartílago, hueso subcondral y en tejido conectivo perivascular del cóndilo articular mandibular (Rabie et al., 2002; 2003). "
    International Journal of Morphology 06/2012; 30(2):621-626. DOI:10.4067/S0717-95022012000200043 · 0.32 Impact Factor
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