Future Clinical Use (future + clinical_use)

Distribution by Scientific Domains

Selected Abstracts

Current opportunities and challenges in skeletal muscle tissue engineering

Merel Koning
Abstract The purpose of this article is to give a concise review of the current state of the art in tissue engineering (TE) of skeletal muscle and the opportunities and challenges for future clinical applicability. The endogenous progenitor cells of skeletal muscle, i.e. satellite cells, show a high proneness to muscular differentiation, in particular exhibiting the same characteristics and function as its donor muscle. This suggests that it is important to use an appropriate progenitor cell, especially in TE facial muscles, which have a exceptional anatomical and fibre composition compared to other skeletal muscle. Muscle TE requires an instructive scaffold for structural support and to regulate the proliferation and differentiation of muscle progenitor cells. Current literature suggests that optimal scaffolding could comprise of a fibrin gel and cultured monolayers of muscle satellite cells obtained through the cell sheet technique. Tissue-engineered muscle constructs require an adequate connection to the vascular system for efficient transport of oxygen, carbon dioxide, nutrients and waste products. Finally, functional and clinically applicable muscle constructs depend on adequate neuromuscular junctions with neural cells. To reach this, it seems important to apply optimal electrical, chemotropic and mechanical stimulation during engineering and discover other factors that influence its formation. Thus, in addition to approaches for myogenesis, we discuss the current status of strategies for angiogenesis and neurogenesis of TE muscle constructs and the significance for future clinical use. Copyright © 2009 John Wiley & Sons, Ltd. [source]

In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to chondrocytes

Wei-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]

Curcumin disrupts meiotic and mitotic divisions via spindle impairment and inhibition of CDK1 activity

A. Bielak-Zmijewska
Objectives:, Curcumin, a natural compound, is a potent anti-cancer agent, which inhibits cell division and/or induces cell death. It is believed that normal cells are less sensitive to curcumin than malignant cells; however, the mechanism(s) responsible for curcumin's effect on normal cells are poorly understood. The aim of this study was to verify the hypothesis that curcumin affects normal cell division by influencing microtubule stability, using mouse oocyte and early embryo model systems. Materials and methods:, Maturating mouse oocytes and two-cell embryos were treated with different concentrations of curcumin (10,50 ,m), and meiotic resumption and mitotic cleavage were analysed. Spindle and chromatin structure were visualized using confocal microscopy. In addition, acetylation and in vitro polymerization of tubulin, in the presence of curcumin, were investigated and the damage to double-stranded DNA was studied using ,H2A.X. CDK1 activity was measured. Results and conclusions:, We have shown for the first time, that curcumin, in a dose-dependent manner, delays and partially inhibits meiotic resumption of oocytes and inhibits meiotic and mitotic divisions by causing disruption of spindle structure and does not induce DNA damage. Our analysis indicated that curcumin affects CDK1 kinase activity but does not directly affect microtubule polymerization and tubulin acetylation. As our study showed that curcumin impairs generative and somatic cell division, its future clinical use or of its derivatives with improved bioavailability after oral administration, should take into consideration the possibility of extensive side-effects on normal cells. [source]

The effect of three different calcium phosphate implant coatings on bone deposition and coating resorption: a long-term histological study in sheep

Christian Schopper
Abstract: The present study investigated the hypothesis that hydroxyapatite (HA), tricalcium phosphate (TCP), and a HA-gel coated on endosseous titanium (Ti) implants by spark discharging (SD) and dip coating would achieve predictable osseointegration without evident bioresorption of the coatings on the long term. A costal sheep model was used for the implantation of the HA/SD, HA/TCP/SD, and HA-gel/SD specimens, which were retrieved 6 and 12 months following implantation. HA and Ti coatings on implants obtained by conventional plasma spraying (HA/PS, Ti/PS) were used as controls. Microscopy showed that osseointegration was achieved from all types of implants. No evidence for bioresorption of the HA/SD, HA/TCP/SD, and HA-gel/SD coatings was present but cohesive failure with disruption of the coating/implant interface was seen. A statistical analysis of the histomorphometrical data showed no time-dependent effect, however. HA/PS coatings achieved significantly higher bone,implant contact (BIC) percentages of the total implant surface (toBIC) than the other types of coatings (P=0.01). If the BIC percentages were traced separately for implant portions placed into cortical and cancellous bone (coBIC and caBIC, respectively), detailed analysis showed that the caBIC values of HA-gel/SD and HA/PS coatings were significantly higher than that of the other types of coatings (P=0.01). CaBIC values were highly correlated with toBIC values (P<0.001). The present study showed that the preparation techniques used produced thin, dense, and unresorbable coatings that achieved osseointegration. Compared with the control coatings, however, only HA-gel/SD coating can be recommended from the investigated preparation techniques for a future clinical use if a better coating cohesion is achieved. Résumé L'étude présente a étudié l'hypothèse que le recouvrement par de l'hydroxyapatite, du phosphate tricalcique et un gel d'hydroxyapatite sur les implants en titane par décharges spark et recouvrement par trempage pourrait apporter une ostéïntégration prévisible sans biorésorption importante des recouvrements à long terme. Un modèle de mouton a été utilisé pour l'implantation de spécimens HA/SD, HA/TCP/SD et gel-HA/SD qui ont été enlevés six et douze mois après leur insertion. Les implants recouverts d'hydroxyapatite et de titane obtenus par plasma-spray conventionnel (HA/PS et Ti/PS) ont été utilisés comme contrôles. La microscopie a montré que l'ostéoïntégration a été réalisée pour tous les types d'implants. Aucune évidence pour la biorésorption de HA/SD, HATCP/SD, et gel-HA/SD n'était présente mais un échec de cohésion avec destruction de l'interface implant/recouvrement a été mis en évidence. Une analyse statistique des données histomorphométriques ne montrait cependant aucun effet dépendant du temps. Les recouvrements HA/PS montraient des pourcentages de contact os/implant significativement plus importants de la surface implantaire totale (BIC) que les autres types de recouvrement (p=0,01). Lorsque les pourcentages de contact os-implant étaient lus séparément pour les portions implantaires placées dans l'os cortical ou l'os spongieux (respectivement coBIC et caBIC), l'analyse détaillée montrait que les valeurs caBIC du gel- HA/SD et des recouvrements HA/PS étaient significativement plus importants que dans les autres types de recouvrement (p<0,01). Les valeurs CaBIC étaient en relation étroite avec les valeurs toBIC (p<0,001). L'étude présente a montré que les techniques de préparation utilisées produisaient des recouvrements non-résorbables denses et fins qui permettaient l'ostéoïntégration. Cependant, comparé aux recouvrements contrôles, seul le recouvrement gel-HA/SD pouvait être recommandé avec les techniques de préparation étudiées pour une utilisation clinique future si une cohésion de recouvrement meilleure est assurée. Zusammenfassung Die vorliegende Studie untersuchte die Hypothese, dass Hydroxyapatit, Trikalziumphoshat und ein Hydroxyapatit-Gel als Beschichtung auf enossalen Ti-Implantaten zur voraussagbaren Osseointegration über einen langen Zeitraum ohne Bioresorption der Beschichtung führen. Die Beschichtungen wurden durch Funkenentladung und Tauchbeschichtung aufgetragen. Für die Implantation der HA/SD, HA/TCP/SD und HA-Gel/SD wurde ein Schafmodell verwendet. Die Proben wurden 6 und 12 Monate nach Implantation entnommen. Als Kontrolle dienten Hydroxyapatit- und Titanbeschichtungen (HA/PS und Ti/PS), welche mittels Plasmaspray aufgetragen worden waren. Die mikroskopische Untersuchung zeigte, das bei allen Implantattypen eine Osseointegration erreicht wurde. Bei den HA/SD, HA/TCP und HA-Gel/SD Beschichtungen waren keine Anzeichen von Bioresorption vorhanden, aber es konnten kohäsive Misserfolge mit Abrissen im Bereich der Implantat/Beschichtung-Berührungsfläche gesehen werden. Eine statistische Analyse der histomorphometrischen Daten zeigte jedoch keinen zeitabhängigen Effekt. Die HA/PS Beschichtungen erreichten signifikant höhere Knochen-Implantat-Kontakt Prozentwerte der gesamten Implantatoberfläche (toBIC) als die anderen Beschichtungen (P=0.01). Wenn die Knochen-Implantat-Kontakt Prozentwerte für Implantatbereiche, welche im kortikalen und spongiösen Knochen (coBIC und caBIC) lagen, separat ausgemessen wurden, so zeigte die detaillierte Analyse, dass die caBIC Werte von HA-Gel/SD und HA/PS Beschichtungen signifikant höher waren als bei allen anderen Typen von Beschichtungen (P=0.01). Die caBIC Werte zeigten eine starke Korrelation mit den toBIC Werten (P<0.001). Die Studie zeigte, dass das verwendete Herstellungsverfahren dünne, dichte und nicht resorbierbare Beschichtungen ergab, welche eine Osseointegration erreichten. Im Vergleich mit den Kontrollbeschichtungen können jedoch nur die HA-Gel/SD Beschichtungen der untersuchten Herstellungsverfahren für den weiteren klinischen Gebrauch empfohlen werden, falls eine bessere Kohäsion der Beschichtung erreicht werden kann. Resumen El presente estudio investigó la hipótesis de que la hidroxiapatita, el fosfato tricálcico y un gel de hidroxiapatita cubriendo implantes endoóseos de Ti por medio de chisporroteo e inmersión pueden lograr una osteointegración predecible sin una biorreabsorción evidente de las cubiertas a largo plazo. Se usó un modelo costal de oveja para la implantación de especímenes HA/SD, HA/TCP/SD, y gel-HA/SD que se retiraron a los 6 y a los 12 meses de la implantación. Como control se usaron cubiertas de hidroxiapatita y titanio en implantes obtenidos por medio de pulverización de plasma convencional (HA/SD, Ti/PS). La microscopía demostró que la osteointegración se logró en todos los tipos de implantes. No existió evidencia de biorreabsorción de las cubiertas HA/SD, HA/TCP/SD, y gel-HA/SD pero se observó fallos en la cohesión con disrupción de la interfase cubierta/implante. Un análisis estadístico de los datos histomorfométricos no mostró, sin embargo efectos dependientes del tiempo. Las cubiertas HA/PS lograron unos porcentajes de contacto hueso-implante significativamente mayores del total de la superficie del implante (toBIC) que los otros tipos de cubiertas (P=0.01). Si se ubicaran los porcentajes de contacto hueso-implante separadamente para porciones situadas dentro de hueso cortical o esponjoso (coBIC y caBIC respectivamente), un análisis detallado mostró que los valores caBIC de las cubiertas de HA-gel/SD y HA/PS fueron significativamente mayores que aquellos de los otros tipos de cubiertas (P<0.001). El presente estudio mostró que las técnicas de preparación usadas produjeron cubiertas finas, densas y no reabsorbibles que alcanzaron la osteointegración. De todos modos, comparadas con las cubiertas de control, solo la cubierta HA-gel/SD pude ser recomendada desde las técnicas de preparación investigadas para un futuro uso clínico si se lograse una mejor cohesión de cubierta. [source]