|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | [Stem cells in the amniotic fluid: the new chance of regenerative medicine]. Orv Hetil. 2011 Apr 10;152(15):581-7 Authors: Joó JG Amniotic fluid has been used in prenatal diagnosis for more than decades. It yields a simple and reliable screening and diagnostic tool for a variety of congenital malformations and genetic diseases such as chromosomal aberrations, neural tube defects or storage diseases. Nowadays the widening knowledge provides evidence that amniotic fluid is not only a screening and diagnostic tool, but it may be also the source of the effective therapy of several congenital and adult disorders. A subset of cells, the so-called stem cells were found in the amniotic fluid as well as the placenta, and they proved to be capable of maintaining prolonged undifferentiated proliferation. Stem cells are able to differentiate into multiple tissue types, originating from the three germ layers. In the near future stem cells isolated from amniotic fluid or placenta and stored by cryopreservation may play a significant role in regenerative medicine. Congenital malformations as well as certain diseases in adults might be treated by tissues coming from progenitor cells of amniotic fluid stem cell origin. This study gives a summary of the main characteristics of amniotic fluid stem cells and it also presents important examples of their possible clinical application. PMID: 21436022 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Development of a novel automated cell isolation, expansion, and characterization platform. J Lab Autom. 2011 Jun;16(3):204-13 Authors: Franscini N, Wuertz K, Patocchi-Tenzer I, Durner R, Boos N, Graf-Hausner U Implementation of regenerative medicine in the clinical setting requires not only biological inventions, but also the development of reproducible and safe method for cell isolation and expansion. As the currently used manual techniques do not fulfill these requirements, there is a clear need to develop an adequate robotic platform for automated, large-scale production of cells or cell-based products. Here, we demonstrate an automated liquid-handling cell-culture platform that can be used to isolate, expand, and characterize human primary cells (e.g., from intervertebral disc tissue) with results that are comparable to the manual procedure. Specifically, no differences could be observed for cell yield, viability, aggregation rate, growth rate, and phenotype. Importantly, all steps-from the enzymatic isolation of cells through the biopsy to the final quality control-can be performed completely by the automated system because of novel tools that were incorporated into the platform. This automated cell-culture platform can therefore replace entirely manual processes in areas that require high throughput while maintaining stability and safety, such as clinical or industrial settings. PMID: 21609703 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A dual acting compound releasing nitric oxide (NO) and ibuprofen, NCX 320, shows significant therapeutic effects in a mouse model of muscular dystrophy. Pharmacol Res. 2011 May 12; Authors: Sciorati C, Miglietta D, Buono R, Pisa V, Cattaneo D, Azzoni E, Brunelli S, Clementi E A resolutive therapy for muscular dystrophies, a heterogeneous group of genetic diseases leading to muscular degeneration and in the severe forms to death, is still lacking. Since inflammation and defects in nitric oxide generation are recognized key pathogenic events in muscular dystrophy, we have analysed the effects of a derivative of ibuprofen, NCX 320, belonging to the class of cyclooxygenase inhibiting nitric oxide donator (CINOD), in the α-sarcoglycan null mice, a severe mouse model of dystrophy. NCX 320 was administered daily in the diet for 8months starting 1month from weaning. Muscle functional recovery was evaluated by free wheel and treadmill tests at 8months. Serum creatine kinase activity, as well as the number of diaphragm inflammatory infiltrates and necrotic fibres, was measured as indexes of skeletal muscle damage. Muscle regeneration was evaluated in diaphragm and tibialis anterior muscles, measuring the numbers of centronucleated fibres and of myogenic precursor cells. NCX 320 mitigated muscle damage, reducing significantly serum creatine kinase activity, the number of necrotic fibres and inflammatory infiltrates. Moreover, NCX 320 stimulated muscle regeneration increasing significantly the number of myogenic precursor cells and regenerating fibres. All these effects concurred in inducing a significant improvement of muscle function, as assessed by both free wheel and treadmill tests. These results describe the properties of a new compound incorporating nitric oxide donation together with anti-inflammatory properties, showing that it is effective in slowing muscle dystrophy progression long term. Of importance, this new compound deserves specific attention for its potential in the therapy of muscular dystrophy given that ibuprofen is well tolerated in paediatric patients and with a profile of safety that makes it suitable for chronic treatment such as the one required in muscular dystrophies. PMID: 21609764 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of early and late effects into the acute spinal cord injury of an injectable functionalized self-assembling scaffold. PLoS One. 2011;6(5):e19782 Authors: Cigognini D, Satta A, Colleoni B, Silva D, Donegà M, Antonini S, Gelain F The complex physiopathological events occurring after spinal cord injury (SCI) make this devastating trauma still incurable. Self-assembling peptides (SAPs) are nanomaterials displaying some appealing properties for application in regenerative medicine because they mimic the structure of the extra-cellular matrix (ECM), are reabsorbable, allow biofunctionalizations and can be injected directly into the lesion. In this study we evaluated the putative neurorigenerative properties of RADA16-4G-BMHP1 SAP, proved to enhance in vitro neural stem cells survival and differentiation. This SAP (RADA16-I) has been functionalized with a bone marrow homing motif (BMHP1) and optimized via the insertion of a 4-glycine-spacer that ameliorates scaffold stability and exposure of the biomotifs. We injected the scaffold immediately after contusion in the rat spinal cord, then we evaluated the early effects by semi-quantitative RT-PCR and the late effects by histological analysis. Locomotor recovery over 8 weeks was assessed using Basso, Beattie, Bresnahan (BBB) test. Gene expression analysis showed that at 7 days after lesion the functionalized SAP induced a general upregulation of GAP-43, trophic factors and ECM remodelling proteins, whereas 3 days after SCI no remarkable changes were observed. Hystological analysis revealed that 8 weeks after SCI our scaffold increased cellular infiltration, basement membrane deposition and axon regeneration/sprouting within the cyst. Moreover the functionalized SAP showed to be compatible with the surrounding nervous tissue and to at least partially fill the cavities. Finally SAP injection resulted in a statistically significant improvement of both hindlimbs' motor performance and forelimbs-hindlimbs coordination. Altogether, these results indicate that RADA16-4G-BMHP1 induced favourable reparative processes, such as matrix remodelling, and provided a physical and trophic support to nervous tissue ingrowth. Thus this biomaterial, eventually combined with cells and growth factors, may constitute a promising biomimetic scaffold for regenerative applications in the injured central nervous system. PMID: 21611127 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Translating stem cell studies to the clinic for CNS repair: current state of the art and the need for a rosetta stone. Neuron. 2011 May 26;70(4):597-613 Authors: Aboody K, Capela A, Niazi N, Stern JH, Temple S Since their discovery twenty years ago and prospective isolation a decade later, neural stem cells (NSCs), their progenitors, and differentiated cell derivatives along with other stem-cell based strategies have advanced steadily toward clinical trials, spurred by the immense need to find reparative therapeutics for central nervous system (CNS) diseases and injury. Current phase I/II trials using stem cells in the CNS are the vanguard for the widely anticipated next generation of regenerative therapies and as such are pioneering the stem cell therapy process. While translation has typically been the purview of industry, academic researchers are increasingly driven to bring their findings toward treatments and face challenges in knowledge gap and resource access that are accentuated by the unique financial, manufacturing, scientific, and regulatory aspects of cell therapy. Solutions are envisioned that both address the significant unmet medical need and lead to increased funding for basic and translational research. PMID: 21609819 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose tissue-derived mesenchymal stem cells and hepatic differentiation: old concepts and future perspectives. Eur Rev Med Pharmacol Sci. 2011 Apr;15(4):355-64 Authors: Puglisi MA, Saulnier N, Piscaglia AC, Tondi P, Agnes S, Gasbarrini A Mesenchymal stem cells (MSCs) are multipotent cells, able to differentiate into elements of the mesodermal lineage. Bone marrow and adipose tissue represent the main sources for MSC isolation. In the last decade, several studies have reported the plasticity of MSCs toward a hepatocyte-like phenotype. The use of MSCs to generate hepatocyte-like cells holds great promises to overcome the scarcity of available organs for transplantation. However, little is known about the molecular pathways involved in lineage cross-differentiation and several issues remain to be answered before MSC application in clinical settings. Aim of this review is to critically analyze the possible sources of MSCs suitable for liver repopulation and the molecular mechanisms underlying MSC hepatic differentiation. PMID: 21608430 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Retinoic acid promotes neural conversion of mouse embryonic stem cells in adherent monoculture. Mol Biol Rep. 2011 May 25; Authors: Xu J, Wang H, Liang T, Cai X, Rao X, Huang Z, Sheng G Retinoic acid (RA) plays multiple roles in the nervous system, including induction of neural differentiation, axon outgrowth and neural patterning. Previously, RA for neural differentiation of embryonic stem (ES) cells always relies on embryoid bodies (EBs) formation. Here we report an in vitro adherent monoculture system to induce mouse ES cells into neural cells accompanied with RA. RA (1 μM) treatment, during initial 2 days of differentiation, can enhance the expression of neural markers, such as Nestin, Tuj1 and MAP2, and result in an earlier neural differentiation of ES cells. Furthermore, RA promotes a significant increase in neurite elongation of ES-derived neurons. Our study also implies that RA induced to express Wnt antagonist Dickkopf-1 (Dkk-1) for neural differentiation. However, the mechanisms of RA triggering neural induction remain to be determined. Our simple and efficient strategy is proposed to provide a basis for studying RA signaling pathways in neural differentiation in vitro. PMID: 21611753 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Poloxamer-188 reduces muscular edema after tourniquet-induced ischemia-reperfusion injury in rats. J Trauma. 2011 May;70(5):1192-7 Authors: Walters TJ, Mase VJ, Roe JL, Dubick MA, Christy RJ : Skeletal muscle injury can result in significant edema, which can in turn lead to the development of acute extremity compartment syndrome (CS). Poloxamer-188 (P-188), a multiblock copolymer surfactant, has been shown to decrease edema by sealing damaged membranes in a number of tissues after a variety of injury modalities. The objective is to determine whether the administration of P-188 significantly reduces skeletal muscle edema associated with ischemia/reperfusion injury (I-R). PMID: 21610433 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Carbohydrate-mediated inhibition of ice recrystallization in cryopreserved human umbilical cord blood. Carbohydr Res. 2011 Jan 3;346(1):86-93 Authors: Wu LK, Tokarew JM, Chaytor JL, von Moos E, Li Y, Palii C, Ben RN, Allan DS Cryopreservation of human umbilical cord blood (UCB) typically involves the cryoprotectant dimethylsulfoxide (DMSO), however, infusional toxicity and reductions in cell viability remain a concern. Ice recrystallization (IR) is an important source of cryopreservation-induced cellular injury and limits the stem cell dose in UCB units. Carbohydrates have wide-ranging intrinsic IR inhibition (IRI) activity related to structural properties. We investigated the impact of carbohydrate IRI on cell viability, induction of apoptosis and hematopoietic progenitor function in cryopreserved UCB. Mononuclear cells (MNCs) from UCB were cryopreserved in storage media containing specific carbohydrates (200mM) and compared to 5% DMSO. Samples were analyzed under conditions of high IR ('slow' thaw) and low IR ('fast' thaw). Thawed samples were analyzed for viability and apoptosis by flow cytometry and hematopoietic function using colony-forming unit (CFU) assays. IRI of carbohydrate solutions was determined using the 'splat cooling' assay. Greater IRI capacity of carbohydrates correlated with increased yield of viable MNCs (r(2)=0.92, p=0.004) and CD34(+) cells (r(2)=0.96, p=0.019) after thawing under conditions of high IR. The correlations were less apparent under conditions of low IR. Carbohydrates with greater IRI modulate the induction of early apoptosis during thawing, especially in CD34+ cells (r(2)=0.96, p=0.0001) as compared to total mononuclear cells (p=0.006), and preserve CFU capacity in vitro (r(2)=0.92, p=<0.0001). Our results suggest that carbohydrates with potent IRI increase the yield of non-apoptotic and functional hematopoietic progenitors and provide a foundation for the development of novel synthetic carbohydrates with enhanced IRI properties to improve cryopreservation of UCB. PMID: 21075361 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Global challenges in stem cell research and the many roads ahead. Neuron. 2011 May 26;70(4):573-6 Authors: Sipp D The field of stem cell research has grown to include a vibrant international community of scientists and clinicians who come from both academia and industry and who strive to shed light on the biology of these remarkable cells and find applications in drug discovery, disease modeling, and regenerative medicine. PMID: 21609815 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3. J Cell Sci. 2011 May 24; Authors: Bone HK, Nelson AS, Goldring CE, Tosh D, Welham MJ The use of small molecules to 'chemically direct' differentiation represents a powerful approach to promote specification of embryonic stem cells (ESCs) towards particular functional cell types for use in regenerative medicine and pharmaceutical applications. Here, we demonstrate a novel route for chemically directed differentiation of human ESCs (hESCs) into definitive endoderm (DE) exploiting a selective small-molecule inhibitor of glycogen synthase kinase 3 (GSK-3). This GSK-3 inhibitor, termed 1m, when used as the only supplement to a chemically defined feeder-free culture system, effectively promoted differentiation of ESC lines towards primitive streak (PS), mesoderm and DE. This contrasts with the role of GSK-3 in murine ESCs, where GSK-3 inhibition promotes pluripotency. Interestingly, 1m-mediated induction of differentiation involved transient NODAL expression and Nodal signalling. Prolonged treatment of hESCs with 1m resulted in the generation of a population of cells displaying hepatoblast characteristics, that is expressing α-fetoprotein and HNF4α. Furthermore, 1m-induced DE had the capacity to mature and generate hepatocyte-like cells capable of producing albumin. These findings describe, for the first time, the utility of GSK-3 inhibition, in a chemically directed approach, to a method of DE generation that is robust, potentially scalable and applicable to different hESC lines. PMID: 21610099 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Treatment of periodontal defects in dogs using an injectable composite hydrogel/biphasic calcium phosphate. J Mater Sci Mater Med. 2011 May 25; Authors: Struillou X, Boutigny H, Badran Z, Fellah BH, Gauthier O, Sourice S, Pilet P, Rouillon T, Layrolle P, Weiss P, Soueidan A An injectable composite silanized hydroxypropyl methyl cellulose/biphasic calcium phosphate (Si-HPMC/BCP) has been investigated in humans with promising results. The aim of this study was to evaluate his efficacy for treating periodontal defects (canine fenestration and premolar furcation) in dog models. At 3 months, we observed that bone formation around BCP particles in furcation model is more discernible but not statistically significant in defects filled with Si-HPMC/BCP compared to healing in control. We suggest that BCP particles sustain the bone healing process by osteoconduction, while the Si-HPMC hydrogel enhances intergranular cohesion and acts as an exclusion barrier. Furthermore, bone ingrowth is not so distinctive in superficial defects where the biomaterial appears unstable. These results with Si-HPMC/BCP are encouraging. In addition, this biomaterial is easy to use and simplifies the process of filling periodontal lesions. However, more researches are needed to improve the viscosity and hardness to adjust the material to the specificities of periodontal defects. PMID: 21611794 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Defining pluripotent stem cells through quantitative proteomic analysis. Expert Rev Proteomics. 2011 Feb;8(1):29-42 Authors: Reiland S, Salekdeh GH, Krijgsveld J Embryonic stem cells (ESCs) are at the center stage of intense research, inspired by their potential to give rise to all cell types of the adult individual. This property makes ESCs suitable candidates for generating specialized cells to replace damaged tissue lost after injury or disease. However, such clinical applications require a detailed insight of the molecular mechanisms underlying the self-renewal, expansion and differentiation of stem cells. This has gained further relevance since the introduction of induced pluripotent stem cells (iPSCs), which are functionally very similar to ESCs. The key property that iPSCs can be derived from somatic cells lifts some of the major ethical issues related to the need for embryos to generate ESCs. Yet, this has only increased the need to define the similarity of iPSCs and ESCs at the molecular level, both before and after they are induced to differentiate. In this article, we describe the proteomic approaches that have been used to characterize ESCs with regard to self-renewal and differentiation, with an emphasis on signaling cascades and histone modifications. We take this as a lead to discuss how quantitative proteomics can be deployed to study reprogramming and iPSC identity. In addition, we discuss how emerging proteomic technologies can become a useful tool to monitor the (de)differentiation status of ESCs and iPSCs. PMID: 21329426 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | An <i>in vitro</i> model system to quantify stress generation, compaction and retraction in engineered heart valve tissue. Tissue Eng Part C Methods. 2011 May 24; Authors: van Vlimmeren MA, Driessen-Mol A, Oomens C, Baaijens F Autologous heart valve tissue engineering relies on extracellular matrix production by cells seeded into a degrading scaffold material. The cells naturally exert traction forces to their surroundings and due to an imbalance between scaffold, tissue and these traction forces, stress is generated within the tissue. This stress results in compaction during culture and retraction of the leaflets at release of constraints, causing shape loss of the heart valve leaflets. In the present study, an in vitro model system has been developed to quantify stress generation, compaction and retraction during culture and after release of constraints. Tissue engineered (TE) constructs based on PGA/P4HB scaffolds seeded with human vascular-derived cells were cultured for 4 weeks. Compaction in width was measured during culture, stress generation was measured during culture and after release of constraints at week 4, and contraction was measured after release of constraints at week 4. Both compaction and stress generation started after 2 weeks of culture and continued up to week 4. TE constructs compacted up to half of their original width and reached an internal stress of 6-8 kPa at week 4, which resulted in a retraction of 36%. The model system has provided a useful tool to unravel and optimize the balance between the different aspects of TE constructs to develop functional tissue engineered leaflets. PMID: 21609192 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cannulation of the Mouse Submandibular Salivary Gland via the Wharton's Duct. J Vis Exp. 2011;(51): Authors: Kuriki Y, Liu Y, Xia D, Gjerde EM, Khalili S, Mui B, Zheng C, Tran SD Severe salivary gland hypofunction is frequently found in patients with Sjögren's syndrome and those who receiving therapeutic irradiation in their head and neck regions for cancer treatment. Both groups of patients experience symptoms such as xerostomia (dry mouth), dysphagia (impaired chewing and swallowing), severe dental caries, altered taste, oro-pharyngeal infections (candidiasis), mucositis, pain and discomfort. One innovative approach of regenerative medicine for the treatment of salivary gland hypo-function is speculated in RS Redman, E Mezey et al. 2009: stem cells can be directly deposited by cannulation into the gland as a potent method in reviving the functions of the impaired organ. Presumably, the migrated foreign stem cells will differentiate into glandular cells to function as part of the host salivary gland. Also, this cannulation technique is an expedient and effective delivery method for clinical gene transfer application. Here we illustrate the steps involved in performing the cannulation procedure on the mouse submandibular salivary gland via the Wharton's duct (Fig 1). C3H mice (Charles River, Montreal, QC, Canada) are used for this experiment, which have been kept under clean conventional conditions at the McGill University animal resource center. All experiments have been approved by the University Animal Care Committee and were in accordance with the guidelines of the Canadian Council on Animal Care. For this experiment, a trypan blue solution is infused into the gland through the opening of the Wharton's duct using a insulin syringe with a 29-gauge needle encased inside a polyethylene tube. Subsequently, the mouse is dissected to show that the infusions migrated into the gland successfully. PMID: 21610677 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Novel genetic loci associated with prostate cancer in the Japanese population. Asian J Androl. 2011 Jan;13(1):120-1 Authors: Sun Y, Huang JT PMID: 20935669 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tendon-Derived Stem Cells (TDSCs): From Basic Science to Potential Roles in Tendon Pathology and Tissue Engineering Applications. Stem Cell Rev. 2011 May 25; Authors: Lui PP, Chan KM Traditionally, tendons are considered to only contain tenocytes that are responsible for the maintenance, repair and remodeling of tendons. Stem cells, which are termed tendon-derived stem cells (TDSCs), have recently been identified in tendons. This review aims to summarize the current information about the in vitro characteristics of TDSCs, including issues related to TDSC isolation and culture, their cell morphology, immunophenotypes, proliferation and differentiation characteristics and senescence during in vitro passaging. The challenges in studying the functions of these cells are also discussed. The niche where TDSCs resided essentially provides signals that are conducive to the maintenance of definitive stem cell properties of TDSCs. Yet the niche may also induce pathologies by imposing an aberrant function on TDSCs or other targets. The possible niche factors of TDSCs are herein discussed. We presented current evidences supporting the potential pathogenic role of TDSCs in the development of tendinopathy with reference to the recent findings on the altered biological responses of these cells in response to their potential niche factors. The use of resident stem cells may promote engraftment and differentiation of transplanted cells in tendon and tendon-bone junction repair because the tendon milieu is an ideal and familiar environment to the transplanted cells. Evidences are presented to show the potential advantages and results of using TDSCs as a new cell source for tendon and tendon-bone junction repair. Issues pertaining to the use of TDSCs for tissue repair are also discussed. PMID: 21611803 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |  | |  | |  |
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