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Regenerative Therapies (regenerative + therapy)
Selected AbstractsSpatiotemporal Delivery Strategies for Promoting Musculoskeletal Tissue Regeneration,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2009Robert E Guldberg PhD Abstract A primary regenerative medicine strategy is to stimulate or augment endogenous repair mechanisms that promote functional restoration of damaged or degenerated tissues. There is increasing evidence that maximizing the potency of tissue regenerative therapies will require design and development of delivery approaches that provide controlled spatiotemporal release of key signaling molecules. Guidance on which factors to deliver and the timing of delivery is emerging from advances in understanding of critical pathways involved in the development of integrated musculoskeletal tissues. A broad range of biomaterials-based deployment technologies are becoming available that allow controlled spatial presentation and release kinetics of biological cues. The purpose of this perspective article is to review promising spatiotemporal delivery strategies designed to promote functional tissue regeneration with an emphasis on vascularized bone repair. [source] Evaluation of human fetal neural stem/progenitor cells as a source for cell replacement therapy for neurological disorders: Properties and tumorigenicity after long-term in vitro maintenanceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Daisuke Ogawa Abstract It is expected that human neural stem/progenitor cells (hNS/PCs) will some day be used in cell replacement therapies. However, their availability is limited because of ethical issues, so they have to be expanded to obtain sufficient amounts for clinical application. Moreover, in-vitro-maintained hNS/PCs may have a potential for tumorigenicity that could be manifested after transplantation in vivo. In the present study, we demonstrate the in vitro and in vivo properties of long-term-expanded hNS/PCs, including a 6-month bioluminescence imaging (BLI) study of their in vivo tumorigenicity. hNS/PCs cultured for approximately 250 days in vitro (hNS/PCs-250) exhibited a higher growth rate and greater neurogenic potential than those cultured for approximately 500 days in vitro (hNS/PCs-500), which showed greater gliogenic potential. In vivo, both hNS/PCs-250 and -500 differentiated into neurons and astrocytes 4 weeks after being transplanted into the striatum of immunodeficient mice, and hNS/PCs-250 exhibited better survival than hNS/PCs-500 at this time point. We also found that the grafted hNS/PCs-250 survived stably and differentiated properly into neurons and astrocytes even 6 months after the surgery. Moreover, during the 6-month observation period by BLI, we did not detect any evidence of rapid tumorigenic growth of the grafted hNS/PCs, and neither PCNA/Ki67-positive proliferating cells nor significant malignant invasive features were detected histologically. These findings support the idea that hNS/PCs may represent a nontumorigenic, safe, and appropriate cell source for regenerative therapies for neurological disorders. © 2008 Wiley-Liss, Inc. [source] Phenotypic and functional comparison of optimum culture conditions for upscaling of bone marrow-derived mesenchymal stem cellsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 3 2009Rakhi Pal Abstract Human adult bone marrow-derived mesenchymal stem cells (MSCs) are a promising tool in the newly emerging avenue of regenerative medicine. MSCs have already been translated from basic research to clinical transplantation research. However, there is still a lack of consensus on the ideal method of culturing MSCs. Here we have compared different culture conditions of human MSCs with an attempt to preserve their characteristics and multi-lineage differentiation potential. We compare the different basal culture media DMEM-F12, DMEM-high glucose (DMEM-HG), DMEM-low glucose (DMEM-LG), knock-out DMEM (DMEM-KO) and Mesencult® on the proliferation rate, surface markers and differentiation potentials of MSCs. At every fifth passage until the 25th passage, the differentiation potential and the presence of a panel of surface markers was observed, using flow cytometry. We also compared the characteristics of human MSCs when cultured in reduced concentrations of fetal bovine serum (FBS), knockout serum replacement (KO-SR) and human plasma. Data indicate that the presence of serum is essential to sustain and propagate MSCs cultures. The choice of basal medium is equally important so as to preserve their characteristics and multipotent properties even after prolonged culture in vitro. With MSCs emerging as a popular tool for regenerative therapies in incurable diseases, it is essential to be able to obtain a large number of MSCs that continue to preserve their characteristics following passaging. The data reveal the optimum basal medium for prolonged culture of MSCs while retaining their ability to differentiate and hence this may be used for up-scaling to provide sufficient numbers for transplantation. Copyright © 2009 John Wiley & Sons, Ltd. [source] Review article: Potential cellular therapies for renal disease: Can we translate results from animal studies to the human condition?NEPHROLOGY, Issue 6 2009MELISSA H LITTLE SUMMARY The incidence of chronic kidney disease is increasing worldwide, prompting considerable research into potential regenerative therapies. These have included studies to determine whether an endogenous renal stem cell exists in the postnatal kidney and whether non-renal adult stem cells, such as mesenchymal stem cell, can ameliorate renal damage. Such stem cells will either need to be recruited to the damaged kidney to repair the damage in situ or be differentiated into the desired cell type and delivered into the damaged kidney to subsequently elicit repair without maldifferentiation. To date, these studies have largely been performed using experimental and genetic models of renal damage in rodents. The translation of such research into a therapy applicable to human disease faces many challenges. In this review, we examine which animal models have been used to evaluate potential cellular therapies and how valid these are to human chronic kidney disease. [source] Neurite growth in 3D collagen gels with gradients of mechanical propertiesBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2009Harini G. Sundararaghavan Abstract We have designed and developed a microfluidic system to study the response of cells to controlled gradients of mechanical stiffness in 3D collagen gels. An ,H'-shaped, source,sink network was filled with a type I collagen solution, which self-assembled into a fibrillar gel. A 1D gradient of genipin,a natural crosslinker that also causes collagen to fluoresce upon crosslinking,was generated in the cross-channel through the 3D collagen gel to create a gradient of crosslinks and stiffness. The gradient of stiffness was observed via fluorescence. A separate, underlying channel in the microfluidic construct allowed the introduction of cells into the gradient. Neurites from chick dorsal root ganglia explants grew significantly longer down the gradient of stiffness than up the gradient and than in control gels not treated with genipin. No changes in cell adhesion, collagen fiber size, or density were observed following crosslinking with genipin, indicating that the primary effect of genipin was on the mechanical properties of the gel. These results demonstrate that (1) the microfluidic system can be used to study durotactic behavior of cells and (2) neurite growth can be directed and enhanced by a gradient of mechanical properties, with the goal of incorporating mechanical gradients into nerve and spinal cord regenerative therapies. Biotechnol. Bioeng. 2009;102: 632,643. © 2008 Wiley Periodicals, Inc. [source] Time-lapsed imaging for in-process evaluation of supercritical fluid processing of tissue engineering scaffoldsBIOTECHNOLOGY PROGRESS, Issue 4 2009Melissa L. Mather Abstract This article demonstrates the application of time-lapsed imaging and image processing to inform the supercritical processing of tissue scaffolds that are integral to many regenerative therapies. The methodology presented provides online quantitative evaluation of the complex process of scaffold formation in supercritical environments. The capabilities of the developed system are demonstrated through comparison of scaffolds formed from polymers with different molecular weight and with different venting times. Visual monitoring of scaffold fabrication enabled key events in the supercritical processing of the scaffolds to be identified including the onset of polymer plasticization, supercritical points and foam formation. Image processing of images acquired during the foaming process enabled quantitative tracking of the growing scaffold boundary that provided new insight into the nature of scaffold foaming. Further, this quantitative approach assisted in the comparison of different scaffold fabrication protocols. Observed differences in scaffold formation were found to persist, post-fabrication as evidenced by micro x-ray computed tomography (, x-ray CT) images. It is concluded that time-lapsed imaging in combination with image processing is a convenient and powerful tool to provide insight into the scaffold fabrication process. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Transcription factor HNF and hepatocyte differentiationHEPATOLOGY RESEARCH, Issue 10 2008Masahito Nagaki To know the precise mechanisms underlying the life or death and the regeneration or differentiation of cells would be relevant and useful for the development of a regenerative therapy for organ failure. Liver-specific gene expression is controlled primarily at a transcriptional level. Studies on the transcriptional regulatory elements of genes expressed in hepatocytes have identified several liver-enriched transcriptional factors, including hepatocyte nuclear factor (HNF)-1, HNF-3, HNF-4, HNF-6 and CCAAT/enhancer binding protein families, which are key components of the differentiation process for the fully functional liver. The transcriptional regulation by these HNFs, which form a hierarchical and cooperative network, is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function. Among these liver-enriched transcription factors, HNF-4 is likely to act the furthest upstream as a master gene in transcriptional cascade and interacts with other liver-enriched transcriptional factors to stimulate hepatocyte-specific gene transcription. A link between the extracellular matrix, changes in cytoskeletal filament assembly and hepatocyte differentiation via HNF-4 has been shown to be involved in the transcriptional regulation of liver-specific gene expression. This review provides an overview of the roles of liver-enriched transcription factors in liver function. [source] A subpopulation of mesenchymal stromal cells with high osteogenic potentialJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Hua Liu Abstract Current bone disease therapy with bone marrow-derived mesenchymal stromal cells (MSC) is hampered by low efficiency. Advanced allogeneic studies on well-established mouse genetic and disease models are hindered by difficulties in isolating murine MSC (mMSC). And mMSC prepared from different laboratories exhibit significant heterogeneity. Hence, this study aimed to identify and isolate a sub-population of mMSC at an early passage number with high osteogenic potential. Enrichment of mMSC was achieved by 1-hr silica incubation and negative selection. Approximately 96% of these cells synthesized osteocalcin after 28 days of osteogenic induction in vitro, and displayed a complete dynamic alteration of alkaline phosphatase (ALP) activity with increasing osteogenic maturation and strong mineralization. Moreover, the cells displayed uniform and stable surface molecular profile, long-term survival, fast proliferation in vitro with maintenance of normal karyotype and distinct immunological properties. CD73 was found to be expressed exclusively in osteogenesis but not in adipogenesis. These cells also retained high osteogenic potential upon allogeneic transplantation in an ectopic site by the detection of bone-specific ALP, osteopontin, osteocalcin and local mineralization as early as 12 days after implantation. Hence, these cells may provide a useful source for improving current strategies in bone regenerative therapy, and for characterizing markers defining the putative MSC population. [source] Loss of molars in periodontally treated patients: a retrospective analysis five years or more after active periodontal treatmentJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2006Bettina Dannewitz Abstract Objectives: Evaluation of tooth loss in molars and prognostic factors for molar survival. Material and Methods: Five hundred and five molars in 71 patients (mean age 46 years; 40 females) were evaluated. The following inclusion criteria were required: periodontal therapy of at least one molar, at least 5 years of supportive periodontal therapy, and baseline assessment of furcation involvement (FI). Results: At baseline 200 of 505 molars exhibited no FI, 116 degree I, 122 degree II, and 67 degree III FI. Twenty-seven molars did not receive periodontal treatment; 127 molars were subjected to non-surgical therapy, and 227 to flap surgery. Tunnel preparation was performed on 14 molars, root resection on 20, regenerative therapy on 57 teeth, and 33 molars were extracted. During the average follow-up period of 107 months 38 molars were lost additionally. Molars with degree III FI had the highest mortality. A multi-level proportional hazard model revealed smoking, baseline bone loss, number of molars left, and degree III FI as risk factors influencing the retention time of molars. Conclusion: Overall periodontal therapy results in a good prognosis of molars. Degree III FI leads to a significant deterioration of prognosis. Beyond FI smoking, baseline bone loss, and number of molars left influence molar survival. [source] Modeling normal and pathological processes through skin tissue engineeringMOLECULAR CARCINOGENESIS, Issue 8 2007Marta Garcia Abstract Skin tissue engineering emerged as an experimental regenerative therapy motivated primarily by the critical need for early permanent coverage of extensive burn injuries in patients with insufficient sources of autologous skin for grafting. With time, the approach evolved toward a wider range of applications including disease modeling. We have established a skin-humanized mouse model system consisting in bioengineered human-skin-engrafted immunodeficient mice. This new model allows to performing regenerative medicine, gene therapy, genomics, and pathology studies in a human context on homogeneous samples. Starting from skin cells (keratinocytes and fibroblasts) isolated from normal donor skin or patient's biopsies, we have been able to deconstruct-reconstruct several inherited skin disorders including genodermatoses and cancer-prone diseases in a large number of skin humanized mice. In addition, the model allows conducting studies in normal human skin to gain further insight into physiological processes such as wound healing or UV-responses. © 2007 Wiley-Liss, Inc. [source] | |||||||||||||