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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    • "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.
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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 · 0.20 Impact Factor
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    ABSTRACT: A b s t r a c t I In nt tr ro od du uc ct ti io on n: : Adipose-derived stem cells (ADSCs) have been shown to differentiate into osteoblasts, adipocytes or myoblasts. However, it is not certain that ADSCs are equal to bone marrow stem cells (BMSCs) in their osteogenic differentiation potential. The purpose of this study was to answer the question. M Ma at te er ri ia al l a an nd d m me et th ho od ds s: : Mesenchymal stem cells (MSCs) were isolated from bone marrow and fat of adult rats. After cell expansion in culture media and three passages, osteogenesis was induced on a monolayer culture with osteogenic medium containing dexamethasone, b-glycerophosphate and ascorbate. After 4 weeks, expression of the osteocalcin gene was analyzed by RT-PCR, alkaline phosphatase (ALP) activity assayed, and Alizarin Red S and Von Kossa staining were done. Cell viability and apoptosis were also assayed by MTT and flow cytometry, respectively. R Re es su ul lt ts s: : In the test of osteogenesis, the osteoblastic differentiation of ADSCs as demonstrated by ALP activity was less than that of the BMSCs. The amount of matrix mineralization shown by Alizarin Red S and Von Kossa staining also showed statistical differences between the two MSCs. The incidence of apoptotic cells among ADSCs was higher than BMSCs. The flow cytometry proves that cell growth reduction is due to a decrease of the cells entering the S phase of the cell cycle. The data demonstrated by MTT assay indicated that viable cells among ADSCs were lower than BMSCs in control groups. C Co on nc cl lu us si io on ns s: : The results of our study suggest that ADSCs may have an inferior potential for osteogenesis compared with BMSCs. K Ke ey y w wo or rd ds s: : osteogenesis, bone marrow stem cells, adipose-derived stem cells, rat.
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