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Cartilage Regeneration (cartilage + regeneration)
Selected AbstractsThe Elusive Path to Cartilage RegenerationADVANCED MATERIALS, Issue 32-33 2009Ernst B. Hunziker Abstract Numerous attempts have been made to develop an efficacious strategy for the repair of articular cartilage. These endeavors have been undaunted, if not spurred, by the challenge of the task and by the largely disappointing outcomes in animal models. Of the strategies that have been lately applied in a clinical setting, the autologous-chondrocyte-transplantation technique is the most notorious example. This methodology, which was prematurely launched on the clinical scene, was greeted with enthusiasm and has been widely adopted. However, a recent prospective and randomized clinical trial has revealed the approach to confer no advantage over conventional microfracturing. Why is the repair of articular cartilage such a seemingly intractable problem? The root of the evil undoubtedly lies in the tissue's poor intrinsic healing capacity. But the failure of investigators to tackle the biological stumbling blocks systematically rather than empirically is hardly a less inauspicious circumstance. Moreover, it is a common misbelief that the formation of hyaline cartilage per se suffices, whereas to be durable and functionally competent, the tissue must be fully mature. An appreciation of this necessity, coupled with a thorough understanding of the postnatal development of articular cartilage, would help to steer investigators clear of biological cul-de-sacs. [source] Cartilage Regeneration in the Rabbit Nasal Septum,THE LARYNGOSCOPE, Issue 10 2006Meghann L. Kaiser MD Abstract Objective: Rhinoplasty frequently includes harvesting of nasal septal cartilage. The objective of this prospective basic investigation is to determine whether cartilage can regenerate after submucosal resection (SMR) of the nasal septum in the rabbit. Neocartilage formation has not heretofore been described in this model. Methods: By lateral rhinotomy, SMR was performed on 17 rabbits followed by reapproximation of the perichondrium. After 7 months, septi were fixed, sectioned, and examined histologically. Findings were photographed and data tabulated according to location and extent. Results: Sites of matrix-secreting isogenous chondrocyte islands were identified between the perichondrial flaps of every animal, principally in the anterior inferior septum. The width of the islands averaged 190 ,m, and the mean neocartilage height was found to be 840 ,m. The newly formed cartilage consisted of chondrocytes within chondrons and was comparable in shape and structure to native septal cartilage. Conclusions: After SMR, rabbit cartilage tissue can regenerate and form matrix within the potential space created by surgery. The surrounding stem cell-rich perichondrium may be the site of origin for these chondrocytes. These findings suggest that after SMR of the human nasal septum, it may be possible for new cartilage tissue to develop provided the mucosa is well approximated. This biologic effect may be enhanced by insertion of cytokine-rich tissue scaffolds that exploit the native ability of septal perichondrium to regenerate and repair cartilage tissue. [source] Rabbit Ear Cartilage Regeneration With a Small Intestinal Submucosa Graft,THE LARYNGOSCOPE, Issue S102 2004Edmund A. Pribitkin MD Abstract Objectives/Hypothesis: The objective was to demonstrate that interpositional grafting with porcine small intestinal submucosa promotes cartilage regeneration following excision of rabbit auricular cartilage. Study Design: Blinded, controlled study. Methods: Eight New Zealand white rabbits underwent excision of auricular cartilage on two sites with and two sites without preservation of perichondrium. Porcine small intestinal submucosa was implanted into one site with and one site without intact perichondrium. Remaining sites served as control sites. Histological assessment was performed at 3 (n = 4) and 6 (n = 3) months and at 1 year (n = 1) after grafting. Results: Histological evaluation showed cartilage regeneration accompanied by chronic inflammation in areas in which porcine small intestinal submucosa was implanted between layers of intact perichondrium. Other sites failed to show significant cartilage regeneration. Conclusion: The results of the study using porcine small intestinal submucosa as a bioscaffold for cartilage regeneration are promising and justify further animal and human studies. [source] Matrix-induced autologous chondrocyte implantation in sheep: objective assessments including confocal arthroscopyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2008C. W. Jones Abstract The assessment of cartilage repair has largely been limited to macroscopic observation, magnetic resonance imaging (MRI), or destructive biopsy. The aims of this study were to establish an ovine model of articular cartilage injury repair and to examine the efficacy of nondestructive techniques for assessing cartilage regeneration by matrix-induced autologous chondrocyte implantation (MACI). The development of nondestructive assessment techniques facilitates the monitoring of repair treatments in both experimental animal models and human clinical subjects. Defects (Ø 6 mm) were created on the trochlea and medial femoral condyle of 21 sheep randomized into untreated controls or one of two treatment arms: MACI or collagen-only membrane. Each group was divided into 8-, 10-, and 12-week time points. Repair outcomes were examined using laser scanning confocal arthroscopy (LSCA), MRI, histology, macroscopic ICRS grading, and biomechanical compression analysis. Interobserver analysis of the randomized blinded scoring of LSCA images validated our scoring protocol. Pearson correlation analysis demonstrated the correlation between LSCA, MRI, and ICRS grading. Testing of overall treatment effect independent of time point revealed significant differences between MACI and control groups for all sites and assessment modalities (Asym Sig,<,0.05), except condyle histology. Biomechanical analysis suggests that while MACI tissue may resemble native tissue histologically in the early stages of remodeling, the biomechanical properties remain inferior at least in the short term. This study demonstrates the potential of a multisite sheep model of articular cartilage defect repair and its assessment via nondestructive methods. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:292,303, 2008 [source] Repair of porcine articular cartilage defect with a biphasic osteochondral composite,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2007Ching-Chuan Jiang Abstract Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with ,-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress,relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1277,1290, 2007 [source] Temporal effects of cell adhesion on mechanical characteristics of the single chondrocyteJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2003Wei Huang Abstract Cell adhesion to material surfaces is a fundamental phenomenon in tissue response to implanted devices, and an important consideration in tissue engineering. For example, elucidation of phenomena associated with adhesion of chondrocytes to biomaterials is critical in addressing the difficult problem of articular cartilage regeneration. The first objective of this study was to measure the mechanical adhesiveness characteristics of individual rabbit articular chondrocytes as a function of seeding time to provide further understanding of the cell adhesion process. The second objective was to quantify the force required to separate the plasma membrane from the underlying cytoskeleton as a function of seeding time. After culturing chondrocytes on glass coverslips for 1, 2, 4, 6 h, two biomechanical tests were performed on single chondrocytes: (i) mechanical adhesiveness measurement by the cytodetacher; and (ii) plasma membrane tether formation force measurement by optical tweezers. Cell mechanical adhesiveness increased from 231 ± 149 Pa at 1 h to 1085 ± 211 Pa at 6 h. The cell contact area with the substrata increased from 161 ± 52 ,m2 at 1 h to 369 ± 105 ,m2 at 6 h. The tether formation force increased from 232 ± 23 pN at 1 h to 591 ± 17 pN at 6 h. Moreover, fluorescence staining by rhodamine-phalloidin demonstrated the process of actin spreading within the cytoskeleton from 0.5 to 6 h and allowed for measurement of cell height which was found to decrease from 12.3 ± 2.9 ,m at 0.5 h to 6.2 ± 0.9 ,m at 6 h. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Performance of new gellan gum hydrogels combined with human articular chondrocytes for cartilage regeneration when subcutaneously implanted in nude miceJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 7 2009J. T. Oliveira Abstract Gellan gum is a polysaccharide that has been recently proposed by our group for cartilage tissue-engineering applications. It is commonly used in the food and pharmaceutical industry and has the ability to form stable gels without the use of harsh reagents. Gellan gum can function as a minimally invasive injectable system, gelling inside the body in situ under physiological conditions and efficiently adapting to the defect site. In this work, gellan gum hydrogels were combined with human articular chondrocytes (hACs) and were subcutaneously implanted in nude mice for 4 weeks. The implants were collected for histological (haematoxylin and eosin and Alcian blue staining), biochemical [dimethylmethylene blue (GAG) assay], molecular (real-time PCR analyses for collagen types I, II and X, aggrecan) and immunological analyses (immunolocalization of collagen types I and II). The results showed a homogeneous cell distribution and the typical round-shaped morphology of the chondrocytes within the matrix upon implantation. Proteoglycans synthesis was detected by Alcian blue staining and a statistically significant increase of proteoglycans content was measured with the GAG assay quantified from 1 to 4 weeks of implantation. Real-time PCR analyses showed a statistically significant upregulation of collagen type II and aggrecan levels in the same periods. The immunological assays suggest deposition of collagen type II along with some collagen type I. The overall data shows that gellan gum hydrogels adequately support the growth and ECM deposition of human articular chondrocytes when implanted subcutaneously in nude mice. Copyright © 2009 John Wiley & Sons, Ltd. [source] Progenitor and stem cells for bone and cartilage regenerationJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 5 2009M. K. El Tamer Abstract Research in regenerative medicine is developing at a significantly quick pace. Cell-based bone and cartilage replacement is an evolving therapy aiming at the treatment of patients who suffer from limb amputation, damaged tissues and various bone and cartilage-related disorders. Stem cells are undifferentiated cells with the capability to regenerate into one or more committed cell lineages. Stem cells isolated from multiple sources have been finding widespread use to advance the field of tissue repair. The present review gives a comprehensive overview of the developments in stem cells originating from different tissues and suggests future prospects for functional bone and cartilage tissue regeneration. Copyright © 2009 John Wiley & Sons, Ltd. [source] Sheep embryonic stem-like cells transplanted in full-thickness cartilage defectsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 3 2009Maria Dattena Abstract Articular cartilage regeneration is limited. Embryonic stem (ES) cell lines provide a source of totipotent cells for regenerating cartilage. Anatomical, biomechanical, physiological and immunological similarities between humans and sheep make this animal an optimal experimental model. This study examines the repair process of articular cartilage in sheep after transplantation of ES-like cells isolated from inner cell masses (ICMs) derived from in vitro -produced (IVP) vitrified embryos. Thirty-five ES-like colonies from 40 IVP embryos, positive for stage-specific embryonic antigens (SSEAs), were pooled in groups of two or three, embedded in fibrin glue and transplanted into osteochondral defects in the medial femoral condyles of 14 ewes. Empty defect (ED) and cell-free glue (G) in the controlateral stifle joint served as controls. The Y gene sequence was used to detect ES-like cells in the repair tissue by in situ hybridization (ISH). Two ewes were euthanized at 1 month post-operatively, three each at 2 and 6 months and four at 12 months. Repairing tissue was examined by biomechanical, macroscopic, histological, immunohistochemical (collagen type II) and ISH assays. Scores of all treatments showed no statistical significant differences among treatment groups at a given time period, although ES-like grafts showed a tendency toward a better healing process. ISH was positive in all ES-like specimens. This study demonstrates that ES-like cells transplanted into cartilage defects stimulate the repair process to promote better organization and tissue bulk. However, the small number of cells applied and the short interval between surgery and euthanasia might have negatively affected the results. Copyright © 2009 John Wiley & Sons, Ltd. [source] Co-culture in cartilage tissue engineeringJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 3 2007Jeanine Hendriks Abstract For biotechnological research in vitro in general and tissue engineering specifically, it is essential to mimic the natural conditions of the cellular environment as much as possible. In choosing a model system for in vitro experiments, the investigator always has to balance between being able to observe, measure or manipulate cell behaviour and copying the in situ environment of that cell. Most tissues in the body consist of more than one cell type. The organization of the cells in the tissue is essential for the tissue's normal development, homeostasis and repair reaction. In a co-culture system, two or more cell types brought together in the same culture environment very likely interact and communicate. Co-culture has proved to be a powerful in vitro tool in unravelling the importance of cellular interactions during normal physiology, homeostasis, repair and regeneration. The first co-culture studies focused mainly on the influence of cellular interactions on oocytes maturation to a pre-implantation blastocyst. Therefore, a brief overview of these studies is given here. Later on in the history of co-culture studies, it was applied to study cell,cell communication, after which, almost immediately as the field of tissue engineering was recognized, it was introduced in tissue engineering to study cellular interactions and their influence on tissue formation. This review discusses the introduction and applications of co-culture systems in cell biology research, with the emphasis on tissue engineering and its possible application for studying cartilage regeneration. Copyright © 2007 John Wiley & Sons, Ltd. [source] Gene therapy for cartilage defectsTHE JOURNAL OF GENE MEDICINE, Issue 12 2005Magali Cucchiarini Abstract Focal defects of articular cartilage are an unsolved problem in clinical orthopaedics. These lesions do not heal spontaneously and no treatment leads to complete and durable cartilage regeneration. Although the concept of gene therapy for cartilage damage appears elegant and straightforward, current research indicates that an adaptation of gene transfer techniques to the problem of a circumscribed cartilage defect is required in order to successfully implement this approach. In particular, the localised delivery into the defect of therapeutic gene constructs is desirable. Current strategies aim at inducing chondrogenic pathways in the repair tissue that fills such defects. These include the stimulation of chondrocyte proliferation, maturation, and matrix synthesis via direct or cell transplantation-mediated approaches. Among the most studied candidates, polypeptide growth factors have shown promise to enhance the structural quality of the repair tissue. A better understanding of the basic scientific aspects of cartilage defect repair, together with the identification of additional molecular targets and the development of improved gene-delivery techniques, may allow a clinical translation of gene therapy for cartilage defects. The first experimental steps provide reason for cautious optimism. Copyright © 2005 John Wiley & Sons, Ltd. [source] Rabbit Ear Cartilage Regeneration With a Small Intestinal Submucosa Graft,THE LARYNGOSCOPE, Issue S102 2004Edmund A. Pribitkin MD Abstract Objectives/Hypothesis: The objective was to demonstrate that interpositional grafting with porcine small intestinal submucosa promotes cartilage regeneration following excision of rabbit auricular cartilage. Study Design: Blinded, controlled study. Methods: Eight New Zealand white rabbits underwent excision of auricular cartilage on two sites with and two sites without preservation of perichondrium. Porcine small intestinal submucosa was implanted into one site with and one site without intact perichondrium. Remaining sites served as control sites. Histological assessment was performed at 3 (n = 4) and 6 (n = 3) months and at 1 year (n = 1) after grafting. Results: Histological evaluation showed cartilage regeneration accompanied by chronic inflammation in areas in which porcine small intestinal submucosa was implanted between layers of intact perichondrium. Other sites failed to show significant cartilage regeneration. Conclusion: The results of the study using porcine small intestinal submucosa as a bioscaffold for cartilage regeneration are promising and justify further animal and human studies. [source] Human articular chondrocytes secrete parathyroid hormone,related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesisARTHRITIS & RHEUMATISM, Issue 9 2010J. Fischer Objective The use of bone marrow,derived mesenchymal stem cells (MSCs) has shown promise in cell-based cartilage regeneration. A yet-unsolved problem, however, is the unwanted up-regulation of markers of hypertrophy, such as alkaline phosphatase (AP) and type X collagen, during in vitro chondrogenesis and the formation of unstable calcifying cartilage at heterotopic sites. In contrast, articular chondrocytes produce stable, nonmineralizing cartilage. The aim of this study was to address whether coculture of MSCs with human articular chondrocytes (HACs) can suppress the undesired hypertrophy in differentiating MSCs. Methods MSCs were differentiated in chondrogenic medium that had or had not been conditioned by parallel culture with HAC pellets, or MSCs were mixed in the same pellet with the HACs (1:1 or 1:2 ratio) and cultured for 6 weeks. Following in vitro differentiation, the pellets were transplanted into SCID mice. Results The gene expression ratio of COL10A1 to COL2A1 and of Indian hedgehog (IHH) to COL2A1 was significantly reduced by differentiation in HAC-conditioned medium, and less type X collagen protein was deposited relative to type II collagen. AP activity was significantly lower (P < 0.05) in the cells that had been differentiated in conditioned medium, and transplants showed significantly reduced calcification in vivo. In mixed HAC/MSC pellets, suppression of AP was dose-dependent, and in vivo calcification was fully inhibited. Chondrocytes secreted parathyroid hormone,related protein (PTHrP) throughout the culture period, whereas PTHrP was down-regulated in favor of IHH up-regulation in control MSCs after 2,3 weeks of chondrogenesis. The main inhibitory effects seen with HAC-conditioned medium were reproducible by PTHrP supplementation of unconditioned medium. Conclusion HAC-derived soluble factors and direct coculture are potent means of improving chondrogenesis and suppressing the hypertrophic development of MSCs. PTHrP is an important candidate soluble factor involved in this effect. [source] Tetracycline-regulated bone morphogenetic protein 2 gene expression in lentivirally transduced primary rabbit chondrocytes for treatment of cartilage defectsARTHRITIS & RHEUMATISM, Issue 7 2010Daniela Wübbenhorst Objective Treatment of cartilage defects is still challenging, primarily because of the poor self-healing capacity of articular cartilage. Gene therapy approaches have gained considerable attention, but, depending on the vector system used, they can lead to either limited or unrestrained gene expression, and therefore regulation of gene expression is necessary. This study was undertaken to construct an efficient tetracycline (Tet),regulated, lentivirally mediated system for the expression of growth factor bone morphogenetic protein 2 (BMP-2) in primary rabbit chondrocytes that will allow for the induction and termination of growth factor gene expression once cartilage regeneration is complete. Methods Chondrogenic ATDC5 cells and primary rabbit chondrocytes were lentivirally transduced with different tetracycline-on (Tet-On),regulated, self-inactivating vectors for the induction of expression of enhanced green fluorescent protein (eGFP) or BMP-2, using either a 1-vector system or a 2-vector system. Results Expression of eGFP was induced on ATDC5 cells and chondrocytes. The highest induction rate and highest level of gene expression were reached when the spleen focus-forming virus long terminal repeat promoter was used to drive the reverse transactivator expression, after the addition of doxycycline, in chondrocytes. An up to 20-fold induction of Tet-mediated BMP-2 expression was observed on ATDC5 cells. The extent of induction and expression level of BMP-2 in chondrocytes were similar between the 1-vector system, and 2-vector system,infected cells (mean ± SD 15.5 ± 1.1 ng/ml and 14.6 ± 0.4 ng/ml, respectively). In addition, prolonged induction and switching-off of BMP-2 expression, as well as repeated induction, were demonstrated. Production of proteoglycans, as shown by Alcian blue staining, demonstrated the functionality of the lentivirally expressed BMP-2 under induced conditions. Conclusion The lentivirally mediated Tet-On system is an effective strategy for efficient, repeatedly inducible expression of BMP-2 in primary rabbit chondrocytes. Therefore, use of this system in in vivo experiments may be a promising approach as a treatment strategy for cartilage defects. [source] Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble flt-1ARTHRITIS & RHEUMATISM, Issue 5 2009Tomoyuki Matsumoto Objective The control of angiogenesis during chondrogenic differentiation is an important issue affecting the use of stem cells in cartilage repair, especially with regard to the persistence of regenerated cartilage. This study was undertaken to investigate the effect of vascular endothelial growth factor (VEGF) stimulation and the blocking of VEGF with its antagonist, soluble Flt-1 (sFlt-1), on the chondrogenesis of skeletal muscle-derived stem cells (MDSCs) in a rat model of osteoarthritis (OA). Methods We investigated the effect of VEGF on cartilage repair in an immunodeficiency rat model of OA after intraarticular injection of murine MDSCs expressing bone morphogenetic protein 4 (BMP-4) in combination with MDSCs expressing VEGF or sFlt-1. Results In vivo, a combination of sFlt-1, and BMP-4,transduced MDSCs demonstrated better repair without osteophyte formation macroscopically and histologically following OA induction, when compared with the other groups. Higher differentiation/proliferation and lower levels of chondrocyte apoptosis were also observed in sFlt-1, and BMP-4,transduced MDSCs compared with a combination of VEGF- and BMP-4,transduced MDSCs or with BMP-4,transduced MDSCs alone. In vitro experiments with mixed pellet coculture of MDSCs and OA chondrocytes revealed that BMP-4,transduced MDSCs produced the largest pellets, which had the highest gene expression of not only type II collagen and SOX9 but also type X collagen, suggesting formation of hypertrophic chondrocytes. Conclusion Our results demonstrate that MDSC-based therapy involving sFlt-1 and BMP-4 repairs articular cartilage in OA mainly by having a beneficial effect on chondrogenesis by the donor and host cells as well as by preventing angiogenesis, which eventually prevents cartilage resorption, resulting in persistent cartilage regeneration and repair. [source] In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to chondrocytesARTHRITIS & RHEUMATISM, Issue 2 2009Wei-Hong Chen Objective Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC),based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration. Methods A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage-forming ability. Results Coculture of hPi-GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor , superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp-hMSCs acquired neocartilage-forming potential within the collagen scaffold. Conclusion These findings help define the molecular markers of chondrogenesis and more accurately delineate the stages of chondrogenesis during chondrocytic differentiation of human MSCs. The results indicate that human MSCs committed to the chondroprogenitor stage of chondrocytic differentiation undergo detailed chondrogenic changes. This model of in vitro chondrogenesis of human MSCs represents an advance in cell-based transplantation for future clinical use. [source] The influence of sex on the chondrogenic potential of muscle-derived stem cells: Implications for cartilage regeneration and repairARTHRITIS & RHEUMATISM, Issue 12 2008Tomoyuki Matsumoto Objective To explore possible differences in muscle-derived stem cell (MDSC) chondrogenic differentiation in vitro and articular cartilage regeneration in vivo between murine male MDSCs (M-MDSCs) and female MDSCs (F-MDSCs). Methods Three different populations of M- and F-MDSCs (n = 3 of each sex) obtained via preplate technique, which separates cells based on their variable adhesion characteristics, were compared for their in vitro chondrogenic potential using pellet culture. Cells were assayed with and without retroviral transduction to express bone morphogenetic protein 4 (BMP-4). The influence of both expression of stem cell marker Sca1 and in vitro expansion on the chondrogenic potential of M- and F-MDSCs was also determined. Additionally, BMP-4,transduced M- and F-MDSCs were applied to a full-thickness articular cartilage defect (n = 5 each) on the femur of a nude rat, and the quality of the repaired tissue was evaluated by macroscopic and histologic examination. Results With and without BMP-4 gene transduction, M-MDSCs produced significantly larger pellets with a richer extracellular matrix, compared with F-MDSCs. Sca1 purification influenced the chondrogenic potential of MDSCs, especially M-MDSCs. Long-term culture did not affect the chondrogenic potential of M-MDSCs but did influence F-MDSCs. M-MDSCs repaired articular cartilage defects more effectively than did F-MDSCs at all time points tested, as assessed both macroscopically and histologically. Conclusion Our findings demonstrate that sex influences the chondrogenic differentiation and articular cartilage regeneration potential of MDSCs. Compared with female MDSCs, male MDSCs display more chondrogenic differentiation and better cartilage regeneration potential. [source] Effects of Composition, Solvent, and Salt Particles on the Physicochemical Properties of Polyglycolide/Poly(lactide- co -glycolide) ScaffoldsBIOTECHNOLOGY PROGRESS, Issue 6 2006Yung-Chih Kuo Polyglycolide (PGA)/poly(lactide- co -glycolide) (PLGA) scaffolds were fabricated by a solvent casting/particulate leaching method using hexafluoroisopropanol (HFIP) or acetone for material dissolution and NaCl particles as porogen. The results revealed that the mechanical strength increased as the PGA percentage in a HFIP-processed scaffold increased. Chemical ingredients did not substantially affect the mechanical strength of acetone-processed scaffolds. Large NaCl particles led to weak mechanical strength, low porosity, and small specific surface area. For a fixed composition, PGA crystals in a HFIP-processed scaffold were smaller than those in an acetone-processed scaffold. High PGA fractions yielded partly fused PGA/PLGA scaffolds. A faster degradation rate of a scaffold could result from a higher PGA percentage, smaller NaCl particles, or the existence of chondrocytes. The combination of PGA and PLGA, which compensated each other for bioactivity, would be beneficial to cartilage regeneration. [source] | |||||||||||||