|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Biomimetic design of artificial micro-vasculatures for tissue engineering. Altern Lab Anim. 2010 Dec;38 Suppl 1:67-79 Authors: Barber RW, Emerson DR Over the last decade, highly innovative micro-fabrication techniques have been developed that are set to revolutionise the biomedical industry. Fabrication processes, such as photolithography, wet and dry etching, moulding, embossing and lamination, have been developed for a range of biocompatible and biodegradable polymeric materials. One area where these fabrication techniques could play a significant role is in the development of artificial micro-vasculatures for the creation of tissue samples for drug screening and clinical applications. Despite the enormous technological advances in the field of tissue engineering, one of the major challenges is the creation of miniaturised fluid distribution networks to transport nutrients and waste products, in order to sustain the viability of the culture. In recent years, there has been considerable interest in the development of microfluidic manifolds that mimic the hierarchical vascular and parenchymal networks found in nature. This article provides an overview of microfluidic tissue constructs, and also reviews the hydrodynamic scaling laws that underpin the fluid mechanics of vascular systems. It shows how Murray's law, which governs the optimum ratio between the diameters of the parent and daughter branches in biological networks, can be used to design the microfluidic channels in artificial vasculatures. It is shown that it is possible to introduce precise control over the shear stress or residence time in a hierarchical network, in order to aid cell adhesion and enhance the diffusion of nutrients and waste products. Finally, the paper describes the hydrodynamic extensions that are necessary in order to apply Murray's law to the rectangular channels that are often employed in artificial micro-vasculatures. PMID: 21275485 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Morphology of Photopolymerized End-linked Poly(ethylene glycol) Hydrogels by Small Angle X-ray Scattering. Macromolecules. 2010 Aug 24;43(16):6861-6870 Authors: Waters DJ, Engberg K, Parke-Houben R, Hartmann L, Ta CN, Toney MF, Frank CW Due to the biocompatibility of poly(ethylene glycol) (PEG), PEG-based hydrogels have attracted considerable interest for use as biomaterials in tissue engineering applications. In this work, we show that PEG-based hydrogels prepared by photopolymerization of PEG macromonomers functionalized with either acrylate or acrylamide end-groups generate networks with crosslink junctions of high functionality. Although the crosslink functionality is not well controlled, the resultant networks are sufficiently well ordered to generate a distinct correlation peak in the small angle x-ray scattering (SAXS) related to the distance between crosslink junctions within the PEG network. The crosslink spacing is a useful probe of the PEG chain conformation within the hydrogel and ranges from approximately 6 to 16 nm, dependent upon both the volume fraction of polymer and the molecular weight of the PEG macromonomers. The presence of a peak in the scattering of photopolymerized PEG networks is also correlated with an enhanced compressive modulus in comparison to PEG networks reported in the literature with much lower crosslink functionality that exhibit no scattering peak. This comparison demonstrates that the method used to link together PEG macromonomers has a critical impact on both the nanoscale structure and the macroscopic properties of the resultant hydrogel network. PMID: 21403767 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Engineered Alginate Hydrogels for Effective Microfluidic Capture and Release of Endothelial Progenitor Cells from Whole Blood. Langmuir. 2011 Mar 14; Authors: Hatch A, Hansmann G, Murthy SK Microfluidic adhesion-based cell separation systems are of interest in clinical and biological applications where small sample volumes must be processed efficiently and rapidly. While the ability to capture rare cells from complex suspensions such as blood using microfluidic systems has been demonstrated, few methods exist for rapid and nondestructive release of the bound cells. Such detachment is critical for applications in tissue engineering and cell-based therapeutics in contrast with diagnostics wherein immunohistochemical, proteomic, and genomic analyses can be carried out by simply lysing captured cells. This paper demonstrates how the incorporation of four-arm amine-terminated poly(ethylene glycol) (PEG) molecules along with antibodies within alginate hydrogels can enhance the ability of the hydrogels to capture endothelial progenitor cells (EPCs) from whole human blood. The hydrogel coatings are applied conformally onto pillar structures within microfluidic channels and their dissolution with a chelator allows for effective recovery of EPCs following capture. PMID: 21401041 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration. J Neurosurg Spine. 2011 Feb;14(2):273-80 Authors: Hegewald AA, Endres M, Abbushi A, Cabraja M, Woiciechowsky C, Schmieder K, Kaps C, Thomé C The object of this study was to characterize the regenerative potential of cells isolated from herniated disc tissue obtained during microdiscectomy. The acquired data could help to evaluate the feasibility of these cells for autologous disc cell transplantation. PMID: 21214312 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A proteomic analysis of engineered tendon formation under dynamic mechanical loading in vitro. Biomaterials. 2011 Mar 12; Authors: Jiang Y, Liu H, Li H, Wang F, Cheng K, Zhou G, Zhang W, Ye M, Cao Y, Liu W, Zou H Previous studies have demonstrated the beneficial effect of mechanical loading on in vitro tendon engineering. To understand the mechanism, human tenocytes and polyglycolic acid long fibers were used for in vitro tendon engineering in a bioreactor system for 12 weeks with and without dynamic loading. The engineered neo-tendons were subjected to proteomic analysis using mass spectrometry along with shotgun strategy. As expected, mechanical loading resulted in a more mature tendon tissue characterized by a firmer tissue texture and densely deposited matrices which formed longitudinally aligned collagen fibers in a highly compact fashion. In contrast, non-loaded neo-tendon revealed loosely and less deposited matrices in a relatively less organized pattern. Proteins isolated from two groups of tissues exhibited similar distribution of isoeletric point and molecular weight indicating the similarity and comparability of the tissue specimens. Further, proteomic analysis showed that total 758 proteins were identified from both groups with 194 and 177 proteins uniquely presented in loaded and non-loaded tendons, respectively. Comparison of loaded and non-loaded tendons revealed 195 significantly up-regulated proteins and 189 significantly down-regulated proteins. The differentially expressed proteins could generally be classified into the categories of extracellular matrix, intra-cellular signaling, cytoskeleton and inflammatory response. Among them, significantly up-regulated collagens I and VI, MMP-14, WNT5A, microfilament molecules and some inflammatory factors suggest that the possible mechanism for this particular biological phenomenon may involve increased production of tendon specific matrices, enhanced cross-link of collagens and other matrix molecules, proper matrix remodeling for tissue maturation and mechanotransduction (including non-canonical Wnt signal pathway) mediated other biological processes. PMID: 21402406 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn. Eye (Lond). 2009 Jun;23(6):1442-50 Authors: Ma DH, Kuo MT, Tsai YJ, Chen HC, Chen XL, Wang SF, Li L, Hsiao CH, Lin KK To access the feasibility of using cultivated oral mucosal epithelial cell transplantation (COMET) for the management of severe corneal burn. PMID: 19373264 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Development of a cell-based diabetic wound assay. Altern Lab Anim. 2010 Dec;38 Suppl 1:45-8 Authors: Stephens P Chronic wounds require prolonged healthcare and adversely affect the quality of life of patients. They are particularly prominent in patients with diabetes, and their relative numbers are set to increase with the rise of diabetes within our population. Research is still needed to understand the factors leading to such wounds, to understand why they persist for such long periods of time, and also to develop new and efficacious treatment strategies. One problem facing this research is a lack of adequate animal models, as the current models do not truly reflect the human condition and often lead to much animal suffering. Hence, over the past four years, our group has been trying to develop a human-based in vitro diabetic wound model, which could be used as a high-throughput screening system to pre-screen potential chronic diabetic wound healing agents and to reduce unnecessary animal pain and suffering. To this end, we have isolated healthy and diseased skin fibroblasts from patient tissue biopsies. Crucially, to create a cell reporter system that can be widely used in the future, the cells were immortalised in order to escape senescence. By using microarray analysis, gene expression pattern differences have been identified between healthy and diseased cells, and disease-specific 'reporter' genes have been selected for further studies. The promoters of these reporter genes have been coupled to fluorescent reporter constructs and inserted back into the diseased fibroblasts, so that we now have proof-of-concept for a real-time diabetic reporter system for future exploitation. PMID: 21275483 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Immobilization of thrombocytes on PCL nanofibres enhances chondrocyte proliferation in vitro. Cell Prolif. 2011 Apr;44(2):183-91 Authors: Jakubova R, Mickova A, Buzgo M, Rampichova M, Prosecka E, Tvrdik D, Amler E Objectives: The aim of this study was to develop functionalized nanofibres as a simple delivery system for growth factors (GFs) and make nanofibre cell-seeded scaffold implants a one-step intervention. Materials and methods: We have functionalized polycaprolactone (PCL) nanofibres with thrombocytes adherent on them. Immobilized, these thrombocytes attached to nanofibre scaffolds were used as a nanoscale delivery system for native (autologous) proliferation and differentiation factors, in vitro. Pig chondrocytes were seeded on the thrombocyte-coated scaffolds and levels of proliferation and differentiation of these cells were compared with those seeded on non-coated scaffolds. Results: Immobilized thrombocytes on PCL nanofibres effectively enhanced chondrocyte proliferation due to time-dependent degradation of thrombocytes and release of their GFs. Conclusions: These simply functionalized scaffolds present new possibilities for nanofibre applications, as smart cell scaffolds equipped with a GF delivery tool. PMID: 21401760 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | New biological solutions for hemodialysis access. J Vasc Access. 2011 Mar 11; Authors: Peck MK, Dusserre N, Zagalski K, Garrido SA, Wystrychowski W, Glickman MH, Chronos NA, Cierpka L, L'heureux N, McAllister TN Since Scribner described the first prosthetic chronic dialysis shunt in 1961, the surgical techniques and strategies to maintain vascular access have improved dramatically. Today, hundreds of thousands of patients worldwide are treated with some combination of native vein fistula, synthetic vascular graft, or synthetic semipermanent catheter. Despite significantly lower efficacy compared with autologous fistulae, the basic materials used for synthetic shunts and catheters have evolved surprisingly slowly. The disparity between efficacy rates and concomitant maintenance costs has driven a strong campaign to decrease the use of synthetic grafts and catheters in favor of native fistulae. Whether arguing the benefits of Fistula First or "Catheter Last," the fact that clinicians are in need of an alternative to expanded polytetrafluoroethylene (ePTFE) is irrefutable. The poor performance of synthetic materials has a significant economic impact as well. End-stage renal disease (ESRD) accounts for approximately 6% of Medicare's overall budget, despite a prevalence of about 0.17%. Of that, 15%-25% is spent on access maintenance, making hemodialysis access a critical priority for Medicare. This clinical and economic situation has spawned an aggressive effort to improve clinical care strategies to reduce overall cost and complications. While the bulk of this effort has historically focused on developing new synthetic biomaterials, more recently, investigators have developed a variety of cell-based strategies to create tissue-engineered vascular grafts. In this article, we review the evolution of the field of cardiovascular tissue engineering. We also present an update on the Lifeline™ vascular graft, an autologous, biological, and tissue-engineered vascular graft, which was the first tissue-engineered graft to be used clinically in dialysis patients. PMID: 21404221 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Prunus mume extract exhibits antimicrobial activity against pathogenic oral bacteria. Int J Paediatr Dent. 2011 Mar 15; Authors: Seneviratne CJ, Wong RW, Hägg U, Chen Y, Herath TD, Lakshman Samaranayake P, Kao R International Journal of Paediatric Dentistry 2011 Objectives. Prunus mume is a common fruit in Asia, which has been used in traditional Chinese medicine. In this study, we focused on the antimicrobial properties of Prunus mume extract against oral pathogens related to dental caries and periodontal diseases. Study design. A total of 15 oral pathogens including Streptococcus mutans, S. sobrinus, S. mitis, S. sanguinis, Lactobacillus acidophilus, P. gingivalis, Aggregatibacter actinomycetemcomitans, and Candida species were included in the study. Initially, agar diffusion assay was performed to screen the antimicrobial activities of Prunus mume extract. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were then determined for sensitive species. Effect of Prunus mume extract on human oral keratinocytes (HOK) viability was also tested. Result. In the agar diffusion assay, drug suspension of 2 g/mL was able to inhibit all the bacterial species tested, but not the fungal species. MIC and MBC range of Prunus mume extract against the oral bacteria was 0.15625-0.0003 g/mL and P. gingivalis being the most susceptible species. Prune extract did not cause any detrimental effect on HOK. Conclusion. Prunus mume extract may be a potential candidate for developing an oral antimicrobial agent to control or prevent dental diseases associated with oral pathogenic bacteria. PMID: 21401748 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Electrospun Hydroxyapatite-Functionalized PLLA Scaffold: Potential Applications in Sternal Bone Healing. Ann Biomed Eng. 2011 Mar 15; Authors: Rainer A, Spadaccio C, Sedati P, De Marco F, Carotti S, Lusini M, Vadalà G, Di Martino A, Morini S, Chello M, Covino E, Denaro V, Trombetta M Sternal synthesis after median sternotomy, a conventional access practice in thoracic and cardiac surgery, is at the basis of severe complications, often impairing the clinical outcome of surgical interventions. In this work, we propose the use of an acellular biomaterial scaffold, to be interposed across the fracture rime during closure operations, directly exposing the biomaterial to bone marrow, in order to expedite healing process. A rabbit model of median sternotomy was performed and an electrospun scaffold composed of a hydroxyapatite-loaded absorbable biopolymer (poly-L: -lactide), shaped into a fibrillar structure, was used. CT follow-up confirmed a complete healing in the scaffold-treated group 1 week before the control. Histological evaluation demonstrated presence of newly formed bone trabeculae among scaffold fibers showing a higher degree of maturity with respect to the control untreated group. The proposed approach is able to both guide a more rapid healing and modulate inflammatory response across the wound site, resulting in improved healing and tissue remodeling with respect to conventional closure technique. PMID: 21404125 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells in endometrium and their role in the pathogenesis of endometriosis. Ann N Y Acad Sci. 2011 Mar;1221(1):10-7 Authors: Figueira PG, Abrão MS, Krikun G, Taylor H The human endometrium is a dynamic tissue that undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus; however, less-committed mesenchymal stem cells may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. Finally, besides progenitor stem cells, recent publications have identified multipotent stem cells in the endometrium. These multipotent stem cells are a readily available source of cells that are useful in tissue engineering and regenerative medicine. Endometrial stem cells have been used to generate chondrocytes, myocytes, neurons, and adiposites in vitro as well as to replace dopaminergic neurons in a murine model of Parkinson's disease. PMID: 21401624 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Nasal Septum Derived Multipotent Progenitors: A Potent Source of Stem Cells. Stem Cells Dev. 2011 Mar 15; Authors: Shafiee A, Kabiri M, Ahmadbeigi N, Oraee Yazdani S, Mojtahed M, Amanpour S, Soleimani M Abstract Thus far autologous adult stem cells have attracted great attention for clinical purposes. In this study we aimed to identify and comprehensively characterize subpopulation of multipotent cells within human nasal septal cartilage. We also conducted a comparative investigation with other well established stem cells such as Bone Marrow-Mesenchymal Stem Cells (BM-MSC), Adipose Tissue-Mesenchymal Stem Cells (AT-MSC) and Unrestricted Somatic Stem Cells (USSC). The isolated clonal population was characterized using immunofluorescence, flowcytometery, reverse transcriptase and real-time PCR. Nasal Septal Progenitors (NSP) expressed critical pluripotency and mesoectodermal stem cell markers. They also shared many characteristics with MSC in expression of CD90, CD105, CD106, CD166, HLA-ABC, and lack of expression of CD34, CD45 and HLA-DR. NSP distinctly presented CD133 (Prominin-1). These cells could proliferate rapidly in vitro with a higher clonogenic potential and showed longer life-span than other studied cells. This population bears some other multipotent properties in showing high capacity to be differentiated into other lineages including chondrocytes, osteocytes and neural-like cell types. Another strong/positive feature of this population was their ability to be safely expanded ex-vivo with no susceptibility to chromosomal abnormality or tumorigenicity both in vitro and in vivo. In conclusion, NSP could be considered as an alternative autologous cell source, which can bring them to the top of therapeutic applications. PMID: 21401444 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Exercise and duchenne muscular dystrophy: Toward evidence-based exercise prescription. Muscle Nerve. 2011 Apr;43(4):464-78 Authors: Markert CD, Ambrosio F, Call JA, Grange RW To develop a rational framework for answering questions about the role of exercise in Duchenne muscular dystrophy (DMD), we focused on five pathophysiological mechanisms and offer brief hypotheses regarding how exercise may beneficially modulate pertinent cellular and molecular pathways. We aimed to provide an integrative overview of mechanisms of DMD pathology that may improve or worsen as a result of exercise. We also sought to stimulate discussion of what outcomes/dependent variables most appropriately measure these mechanisms, with the purpose of defining criteria for well-designed, controlled studies of exercise in DMD. The five mechanisms include pathways that are both intrinsic and extrinsic to the diseased muscle cells. Muscle Nerve 43: 464-478, 2011. PMID: 21404285 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Reconstitution of hepatic tissue architectures from fetal liver cells obtained from a three-dimensional culture with a rotating wall vessel bioreactor. J Biosci Bioeng. 2011 Mar 12; Authors: Ishikawa M, Sekine K, Okamura A, Zheng YW, Ueno Y, Koike N, Tanaka J, Taniguchi H Reconstitution of tissue architecture in vitro is important because it enables researchers to investigate the interactions and mutual relationships between cells and cellular signals involved in the three-dimensional (3D) construction of tissues. To date, in vitro methods for producing tissues with highly ordered structure and high levels of function have met with limited success although a variety of 3D culture systems have been investigated. In this study, we reconstituted functional hepatic tissue including mature hepatocyte and blood vessel-like structures accompanied with bile duct-like structures from E15.5 fetal liver cells, which contained more hepatic stem/progenitor cells comparing with neonatal liver cells. The culture was performed in a simulated microgravity environment produced by a rotating wall vessel (RWV) bioreactor. The hepatocytes in the reconstituted 3D tissue were found to be capable of producing albumin and storing glycogen. Additionally, bile canaliculi between hepatocytes, characteristics of adult hepatocyte in vivo were also formed. Apart from this, bile duct structure secreting mucin was shown to form complicated tubular branches. Furthermore, gene expression analysis by semi-quantitative RT-PCR revealed the elevated levels of mature hepatocyte markers as well as genes with the hepatic function. With RWV culture system, we could produce functionally reconstituted liver tissue and this might be useful in pharmaceutical industry including drug screening and testing and other applications such as an alternative approach to experimental animals. PMID: 21402492 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The modulation of myogenic cells differentiation using a semiconductor-muscle junction. Biomaterials. 2011 Mar 12; Authors: Quarta M, Scorzeto M, Canato M, Maschio MD, Conte D, Blaauw B, Vassanelli S, Reggiani C The present study is aimed to design a prototype of hybrid silicon-muscle cell junction, analog to an artificial neuromuscular junction prototype and relevant to the development of advanced neuro-prostheses and bionic systems. The device achieves focal Electric Capacitive Stimulation (ECS) by coupling of single cells and semiconductors, without electrochemical reaction with the substrate. A voltage change applied to a stimulation spot beneath an electrogenic cell leads to a capacitive current (charge accumulation) that opens voltage-gated ion channels in the membrane and generates an action potential. The myo-electronic junction was employed to chronically stimulate muscle cells via ECS and to induce cytosolic calcium transients in myotubes, fibers isolated from mouse FDB (fast [Ca(2+)](i) transients) and surprisingly also in undifferentiated myoblasts (slow [Ca(2+)](i) waves). The hybrid junction elicited, via chronic ECS, a differential reprogramming of single muscle cells by inducing early muscle contraction maturation and plasticity effects, such as NFAT-C3 nuclear translocation. In addition, in the presence of agrin, chronic ECS induced a modulation of AchR clustering which simulates in vitro synaptogenesis. This methodology can coordinate the myogenic differentiation, thus offering direct but non-invasive single cell/wiring, providing a platform for regenerative medicine strategies. PMID: 21402404 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The Emerging Role of Epigenetics in Stroke: III. Neural Stem Cell Biology and Regenerative Medicine. Arch Neurol. 2011 Mar;68(3):294-302 Authors: Qureshi IA, Mehler MF The transplantation of exogenous stem cells and the activation of endogenous neural stem and progenitor cells (NSPCs) are promising treatments for stroke. These cells can modulate intrinsic responses to ischemic injury and may even integrate directly into damaged neural networks. However, the neuroprotective and neural regenerative effects that can be mediated by these cells are limited and may even be deleterious. Epigenetic reprogramming represents a novel strategy for enhancing the intrinsic potential of the brain to protect and repair itself by modulating pathologic neural gene expression and promoting the recapitulation of seminal neural developmental processes. In fact, recent evidence suggests that emerging epigenetic mechanisms are critical for orchestrating nearly every aspect of neural development and homeostasis, including brain patterning, neural stem cell maintenance, neurogenesis and gliogenesis, neural subtype specification, and synaptic and neural network connectivity and plasticity. In this review, we survey the therapeutic potential of exogenous stem cells and endogenous NSPCs and highlight innovative technological approaches for designing, developing, and delivering epigenetic therapies for targeted reprogramming of endogenous pools of NSPCs, neural cells at risk, and dysfunctional neural networks to rescue and restore neurologic function in the ischemic brain. PMID: 21403016 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells in endometrium and their role in the pathogenesis of endometriosis. Ann N Y Acad Sci. 2011 Mar;1221(1):10-7 Authors: Figueira PG, Abrão MS, Krikun G, Taylor H The human endometrium is a dynamic tissue that undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus; however, less-committed mesenchymal stem cells may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. Finally, besides progenitor stem cells, recent publications have identified multipotent stem cells in the endometrium. These multipotent stem cells are a readily available source of cells that are useful in tissue engineering and regenerative medicine. Endometrial stem cells have been used to generate chondrocytes, myocytes, neurons, and adiposites in vitro as well as to replace dopaminergic neurons in a murine model of Parkinson's disease. PMID: 21401624 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Human Deciduous Teeth Dental Pulp Cells With Basic Fibroblast Growth Factor Enhance Wound Healing of Skin Defect. J Craniofac Surg. 2011 Mar 9; Authors: Nishino Y, Ebisawa K, Yamada Y, Okabe K, Kamei Y, Ueda M In this research, we examined the effect on wound healing applying basic fibroblast growth factor (b-FGF) that is approved for clinical use to enhance wound healing and human deciduous teeth dental pulp cells (hDPCs) in clinics, but that have been attracting attention as a novel stem cell source in recent years. Human deciduous teeth were harvested from healthy volunteers, and hDPCs were isolated. We used a nude mouse full-thickness skin defect model and evaluated wound healing by macroscopic view and histologic and histomorphometric analysis. The mice were randomly divided into 4 groups: phosphate-buffered saline-treated group (control group), b-FGF-treated group (b-FGF group), hDPC-treated group (hDPC group), and hDPC and b-FGF-treated group (hDPC/b-FGF group). Basic fibroblast growth factor and hDPC groups accelerated wound healing compared with the control group. There was no statistically significant difference in wound healing observed between the hDPC and b-FGF groups. The hDPC/b-FGF group demonstrated accelerated wound healing compared with other groups. At day 14, PKH26-positive cells were surrounded by human type I collagen in hDPC and hDPC/b-FGF groups in immunohistologic evaluation. Significantly increased collagen fibril areas in wound tissues were observed in b-FGF, hDPC, and hDPC/b-FGF groups as compared with the control group at days 7 and 14. Our results showed that the hDPC/b-FGF group significantly promotes wound healing compared with other groups. This study implies that deciduous teeth that are currently considered as medical spare parts might offer a unique stem cell resource for potential of new cell therapies for wound healing in combination with b-FGF. PMID: 21403563 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Therapeutic liver repopulation for phenylketonuria. J Inherit Metab Dis. 2010 Dec;33(6):681-7 Authors: Harding CO, Gibson KM Problems with long-term dietary compliance in phenylketonuria (PKU) necessitate the development of alternative treatment approaches. Therapeutic liver repopulation with phenylalanine hydroxylase (PAH)-expressing cells following hepatocyte or haematopoietic stem cell transplantation has been investigated as a possible novel treatment approach for PKU. Successful therapeutic liver repopulation requires both a stimulus for liver regeneration at the time of cell transplantation and a selective growth advantage for the PAH+ donor cells. Unfortunately, wild-type PAH+ hepatocytes do not enjoy any growth advantage over PAH- cells. Successful correction of hyperphenylalaninemia following therapeutic liver repopulation has been accomplished only in an animal model that yields a selective advantage for the donor cells. Haematopoietic stem cell (HSC)-mediated therapeutic liver repopulation has not been reported in any hyperphenylalaninemic system, and the success of HSC-mediated liver repopulation for PKU may be limited by the slow kinetics of this approach. If therapeutic liver repopulation is to be employed successfully in humans with PKU, an effective method of providing a selective growth advantage for the donor cells must be developed. If this can be achieved, liver repopulation with 10-20% wild-type hepatocytes will likely completely normalize Phe clearance in individuals with PKU. PMID: 20495959 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | ZO-1 determines adherens and gap junction localization at intercalated disks. Am J Physiol Heart Circ Physiol. 2011 Feb;300(2):H583-94 Authors: Palatinus JA, O'Quinn MP, Barker RJ, Harris BS, Jourdan J, Gourdie RG The disruption of the spatial order of electromechanical junctions at myocyte-intercalated disks (ICDs) is a poorly understood characteristic of many cardiac disease states. Here, in vitro and in vivo evidence is provided that zonula occludens-1 (ZO-1) regulates the organization of gap junctions (GJs) and adherens junctions (AJs) at ICDs. We investigated the contribution of ZO-1 to cell-cell junction localization by expressing a dominant-negative ZO-1 construct (DN-ZO-1) in rat ventricular myocytes (VMs). The expression of DN-ZO-1 in cultured neonatal VMs for 72 h reduced the interaction of ZO-1 and N-cadherin, as assayed by colocalization and coimmunoprecipitation, prompting cytoplasmic internalization of AJ and GJ proteins. DN-ZO-1 expression in adult VMs in vivo also reduced N-cadherin colocalization with ZO-1, a phenomenon not observed when the connexin-43 (Cx43)-ZO-1 interaction was disrupted using a mimetic of the ZO-1-binding ligand from Cx43. DN-ZO-1-infected VMs demonstrated large GJs at the ICD periphery and showed a loss of focal ZO-1 concentrations along plaque edges facing the disk interior. Additionally, there was breakdown of the characteristic ICD pattern of small interior and large peripheral GJs. Continuous DN-ZO-1 expression in VMs over postnatal development reduced ICD-associated Cx43 GJs and increased lateralized and cytoplasmic Cx43. We conclude that ZO-1 regulation of GJ localization is via an association with the N-cadherin multiprotein complex and that this is a key determinant of stable localization of both AJs and GJs at the ICD. PMID: 21131473 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Inhibition of metastasis-associated gene 1 expression affects proliferation and osteogenic differentiation of immortalized human mesenchymal stem cells. Cell Prolif. 2011 Apr;44(2):128-38 Authors: Kumar A, Salimath BP, Schieker M, Stark GB, Finkenzeller G Objectives: MTA1 is known to be responsible for independent nucleosome remodelling and deacetylase complexes with ability to regulate divergent cellular pathways. However, additional biological functions have, up to now, remained largely unexplored. The present study was initiated to investigate involvement of MTA1 in osteogenic differentiation of immortalized human mesenchymal stem cells (MSCs). Materials and methods: MSCs were examined for expression of MTA1 and stably transfected clones expressing shRNA to MTA1 were generated. Cells were grown under osteogenic and non-osteogenic conditions. Effects of silencing on cell proliferation, calcium deposition and alkaline phosphatase (ALP) activity were studied. mRNA expression of bone sialoprotein (BSP), osteopontin (OSP), runt-related transcription factor 2 (Runx2), osteocalcin (OC), collagen type I (Col1A) and ALP were analysed. Results: Transfected cells showed reduction in proliferation and significant increase in calcium deposition and expression of osteogenic marker genes, BSP, OSP, Runx2, OC and Col1A, when they were grown under osteogenic conditions. Under non-osteogenic conditions, expression of BSP and OSP were also markedly upregulated, whereas expression of osteogenic marker genes, Runx2, OC and Col1A, was almost unaffected. Expression of ALP was slightly suppressed under non-osteogenic conditions but significantly increased under osteogenic differentiation conditions, as assessed by enzyme activity and mRNA expression assays. Conclusions: Our data collectively suggest that endogenously produced MTA1 constrains osteogenic differentiation of MSCs and that targeting of this molecule may provide a novel strategy for enhancing bone regeneration. PMID: 21401754 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | DHEA provides a microenvironment for endometrial stem cells neurogenesis. Med Hypotheses. 2011 Mar 12; Authors: Shoae-Hassani A, Mortazavi-Tabatabaei SA, Sharif S, Rezaei-Khaligh H, Verdi J Recently, transplantation of adult stem cells over embryonic stem cells increased in regenerative medicine. Among the adult stem cells, human endometrium stromal (hEnS) cells are under the strict control of the steroid hormones and have the potential to differentiate into other cell lineages including neural cells. Unfortunately these cells may lose their neurogenic differentiation ability upon extended expansion in cultures. To avoid the back-differentiation, it is important to establish growth conditions that support the rapid proliferation and stable differentiation of hEnS cells over extended periods of time without compromising their neuronal phenotype. Differentiation of transplanted cells is strongly influenced by environmental signals. The steroidal microenvironment of the stem cells plays a major role in controlling neurogenesis in the cultures. Dehydroepiandrosterone (DHEA) administration to the cultures could support this propose. DHEA enhance survival rates of dissociated neurons in cultures. It can activate AKT protein kinase pathway as well as nerve growth factor (NGF) that enhances neurogenesis efficiently. On the other hand it seems that DHEA increase survival rate of neural cells via production of brain derived neurotrophic factor (BDNF), indirectly. BDNF is a mediator product of the DHEA that promotes the differentiation and survival of neurons. Here, we offer that DHEA is a suitable candidate that could provide a microenvironment to stimulate neurogenesis and enhanced survival of newly formed neurons derived from hEnS cells. From the point that DHEA is the most abundant steroid in the body, marketed as a supplement and is increasingly self-prescription we hypothesized that it could be the safe and high available choice. This provides a better insight into the maintenance of neural cells for treatment of a wide variety of neurological diseases such as Alzheimer's and Parkinson's by non-invasively autologous cell therapy by hEnS cells especially in women. PMID: 21402451 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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