Wednesday, January 19, 2011

1/20 TE-RegenMed-StemCell feed

     
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Neuroplasticity in the context of motor rehabilitation after stroke.
January 19, 2011 at 11:17 PM
 

Neuroplasticity in the context of motor rehabilitation after stroke.

Nat Rev Neurol. 2011 Jan 18;

Authors: Dimyan MA, Cohen LG

Approximately one-third of patients with stroke exhibit persistent disability after the initial cerebrovascular episode, with motor impairments accounting for most poststroke disability. Exercise and training have long been used to restore motor function after stroke. Better training strategies and therapies to enhance the effects of these rehabilitative protocols are currently being developed for poststroke disability. The advancement of our understanding of the neuroplastic changes associated with poststroke motor impairment and the innate mechanisms of repair is crucial to this endeavor. Pharmaceutical, biological and electrophysiological treatments that augment neuroplasticity are being explored to further extend the boundaries of poststroke rehabilitation. Potential motor rehabilitation therapies, such as stem cell therapy, exogenous tissue engineering and brain-computer interface technologies, could be integral in helping patients with stroke regain motor control. As the methods for providing motor rehabilitation change, the primary goals of poststroke rehabilitation will be driven by the activity and quality of life needs of individual patients. This Review aims to provide a focused overview of neuroplasticity associated with poststroke motor impairment, and the latest experimental interventions being developed to manipulate neuroplasticity to enhance motor rehabilitation.

PMID: 21243015 [PubMed - as supplied by publisher]

   
   
Preparation and Characterization of a 3D-printed Scaffold Based on a Functionalized Polyester for Bone Tissue Engineering Applications.
January 19, 2011 at 11:17 PM
 

Preparation and Characterization of a 3D-printed Scaffold Based on a Functionalized Polyester for Bone Tissue Engineering Applications.

Acta Biomater. 2011 Jan 14;

Authors: Seyednejad H, Gawlitta D, Dhert WJ, van Nostrum CF, Vermonden T, Hennink WE

At present, there is a strong need for suitable scaffolds that meet the requirements for bone tissue engineering applications. The objective of this study was to investigate the suitability of porous scaffolds based on a hydroxyl functionalized polymer (poly(hydroxymethylglycolide-co-ε-caprolactone), pHMGCL) for tissue engineering. In a recent study, this polymer was shown to be a promising material for bone regeneration. The scaffolds consisting of pHMGCL or poly(ε-caprolactone) (PCL) were produced by means of a rapid prototyping technique (3D plotting) and were shown to have a high porosity and an interconnected pore structure. The thermal and mechanical properties of both scaffolds were investigated and human mesenchymal stem cells were seeded onto the scaffolds to evaluate the cell attachment properties, as well as cell viability and differentiation. It was shown that the cells filled the pores of the pHMGCL scaffold within 7 days and displayed increased metabolic activity when compared with cells cultured in PCL scaffolds. Importantly, pHMGCL scaffolds supported osteogenic differentiation. Therefore, scaffolds based on pHMGCL are promising templates for bone tissue engineering applications.

PMID: 21241834 [PubMed - as supplied by publisher]

   
   
RNA Interference Therapy via Functionalized Scaffolds.
January 19, 2011 at 11:17 PM
 

RNA Interference Therapy via Functionalized Scaffolds.

Adv Drug Deliv Rev. 2011 Jan 14;

Authors: Monaghan M, Pandit A

Tissue engineering aims to provide structural and biomolecular cues to compromised tissues through scaffolds. An emerging biomolecular cue is that of RNA interference by which the expression of genes can be silenced through a potent endogenous pathway. Recombinant viral based approaches in RNAi delivery exist; however non-viral strategies offer many opportunities to exploit this mechanism of regulation in a safer way. Current RNAi therapies in clinical trials are without a vector (naked) or have slightly modified structures. Modification of these molecules with efficient backbone moieties for improved stability and potency, protecting and buffering them with delivery vehicles, and using scaffolds as reservoirs of delivery is at the frontier of current research. However, to enable an efficient sustained therapeutic effect scaffolds have a potentially significant role to play. This review presents non-viral delivery of RNAi that have been attempted via tissue engineered scaffolds. For RNAi to have a clinical impact, it is imperative to evaluate optimal delivery systems to ensure that the efficacy of this promising technology can be maximized.

PMID: 21241760 [PubMed - as supplied by publisher]

   
   
Lessons from (patho)physiological tissue stiffness and their implications for drug screening, drug delivery and regenerative medicine.
January 19, 2011 at 11:17 PM
 

Lessons from (patho)physiological tissue stiffness and their implications for drug screening, drug delivery and regenerative medicine.

Adv Drug Deliv Rev. 2011 Jan 14;

Authors: Chen WL, Simmons CA

Diseased tissues are noted for their compromised mechanical properties, which contribute to organ failure; regeneration entails restoration of tissue structure and thereby functions. Thus, the physical signature of a tissue is closely associated with its biological function. In this review, we consider a mechanics-centric view of disease and regeneration by drawing parallels between in vivo tissue-level observations and corroborative cellular evidence in vitro to demonstrate the importance of the mechanical stiffness of the extracellular matrix in these processes. This is not intended to devalue the importance of biochemical signalling; in fact, as we discuss, many mechanical stiffness-driven processes not only require cooperation with biochemical cues, but they ultimately converge at common signaling cascades to influence cell and tissue function in an integrative manner. The study of how physical and biochemical signals collectively modulate cell function not only brings forth a more holistic understanding of cell (patho)biology, but it also creates opportunities to control material properties to improve culture platforms for research and drug screening and aid in the rationale design of biomaterials for molecular therapy and tissue engineering applications.

PMID: 21241759 [PubMed - as supplied by publisher]

   
   
Skin Tissue Engineering - In Vivo and In Vitro Applications.
January 19, 2011 at 11:17 PM
 

Skin Tissue Engineering - In Vivo and In Vitro Applications.

Adv Drug Deliv Rev. 2011 Jan 14;

Authors: Groeber F, Holeiter M, Hampel M, Hinderer S, Schenke-Layland K

Significant progress has been made over the years in the development of in vitro-engineered substitutes that mimic human skin, either to be used as grafts for the replacement of lost skin or for the establishment of human-based in vitro skin models. This review summarizes these advances in in vivo and in vitro applications of tissue-engineered skin. We further highlight novel efforts in the design of complex disease-in-a-dish models for studies ranging from disease etiology to drug development and screening.

PMID: 21241756 [PubMed - as supplied by publisher]

   
   
Nanotopographic Control of Neuronal Polarity.
January 19, 2011 at 11:17 PM
 

Nanotopographic Control of Neuronal Polarity.

Nano Lett. 2011 Jan 11;

Authors: Ferrari A, Cecchini M, Dhawan A, Micera S, Tonazzini I, Stabile R, Pisignano D, Beltram F

We employ simple geometrical rules to design a set of nanotopographies able to interfere with focal adhesion establishment during neuronal differentiation. Exploiting nanoimprint lithography techniques on cyclic-olefin-copolymer films, we demonstrate that by varying a single topographical parameter the orientation and maturation of focal adhesions can be finely modulated yielding independent control over the final number and the outgrowth direction of neurites. Taken together, this report provides a novel and promising approach to the rational design of biocompatible textured substrates for tissue engineering applications.

PMID: 21241061 [PubMed - as supplied by publisher]

   
   
The restoration of full-thickness cartilage defects with BMSCs and TGF-beta 1 loaded PLGA/fibrin gel constructs.
January 19, 2011 at 11:17 PM
 

The restoration of full-thickness cartilage defects with BMSCs and TGF-beta 1 loaded PLGA/fibrin gel constructs.

Biomaterials. 2010 Dec;31(34):8964-73

Authors: Wang W, Li B, Yang J, Xin L, Li Y, Yin H, Qi Y, Jiang Y, Ouyang H, Gao C

Poly(lactide-co-glycolide) (PLGA) sponge was filled with fibrin gel, bone marrow mesenchymal stem cells (BMSCs) and transforming growth factor-β1 (TGF-β1) to obtain a construct for cartilage restoration in vivo. The PLGA sponge lost its weight steadily in vitro, but degraded much faster in the construct of PLGA/fibrin gel/BMSCs implanted in the full-thickness cartilage defects. The in vivo degradation of the fibrin gel inside the construct was prolonged to 12 wk too. The CM-DiI labeled allogenic BMSCs were detectable after transplantation (implantation) into the defects for 12 wk by small animal in vivo fluorescence imaging and confocal laser scanning microscopy. In vivo repair experiments were firstly performed by implantation of the PLGA/fibrin gel/BMSCs and PLGA/BMSCs constructs into full-thickness cartilage defects (3 mm in diameter and 4 mm in depth) of New Zealand white rabbits for 12 wk. The defects implanted with the PLGA/fibrin gel/BMSCs constructs were filled with cartilage-like tissue containing collagen type II and glycosaminoglycans (GAGs), while those by the PLGA/BMSCs constructs were filled with fibrous-like tissues. To repair the defects of larger size (4 mm in diameter), addition of growth factors was mandatory as exemplified here by further loading of TGF-β1. Implantation of the PLGA/fibrin gel/BMSCs/TGF-β1 constructs into the full-thickness cartilage defects for 12 wk resulted in full restoration of the osteochondral tissue. The neo-cartilage integrated well with its surrounding cartilage and subchondral bone. Immunohistochemical and GAGs staining confirmed the similar distribution of collagen type II and GAGs in the regenerated cartilage as that of hyaline cartilage. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed that the cartilage special genes were significantly up-regulated compared with those of the TGF-β1 absent constructs.

PMID: 20822812 [PubMed - indexed for MEDLINE]

   
   
Viscoelastic and biomechanical properties of osteochondral tissue constructs generated from graded polycaprolactone and beta-tricalcium phosphate composites.
January 19, 2011 at 11:17 PM
 

Viscoelastic and biomechanical properties of osteochondral tissue constructs generated from graded polycaprolactone and beta-tricalcium phosphate composites.

J Biomech Eng. 2010 Sep;132(9):091013

Authors: Erisken C, Kalyon DM, Wang H

The complex micro-/nanostructure of native cartilage-to-bone insertion exhibits gradations in extracellular matrix components, leading to variations in the viscoelastic and biomechanical properties along its thickness to allow for smooth transition of loads under physiological movements. Engineering a realistic tissue for osteochondral interface would, therefore, depend on the ability to develop scaffolds with properly graded physical and chemical properties to facilitate the mimicry of the complex elegance of native tissue. In this study, polycaprolactone nanofiber scaffolds with spatially controlled concentrations of beta-tricalcium phosphate nanoparticles were fabricated using twin-screw extrusion-electrospinning process and seeded with MC3T3-E1 cells to form osteochondral tissue constructs. The objective of the study was to evaluate the linear viscoelastic and compressive properties of the native bovine osteochondral tissue and the tissue constructs formed in terms of their small-amplitude oscillatory shear, unconfined compression, and stress relaxation behavior. The native tissue, engineered tissue constructs, and unseeded scaffolds exhibited linear viscoelastic behavior for strain amplitudes less than 0.1%. Both native tissue and engineered tissue constructs demonstrated qualitatively similar gel-like behavior as determined using linear viscoelastic material functions. The normal stresses in compression determined at 10% strain for the unseeded scaffold, the tissue constructs cultured for four weeks, and the native tissue were 0.87+/-0.08 kPa, 3.59+/-0.34 kPa, and 210.80+/-8.93 kPa, respectively. Viscoelastic and biomechanical properties of the engineered tissue constructs were observed to increase with culture time reflecting the development of a tissuelike structure. These experimental findings suggest that viscoelastic material functions of the tissue constructs can provide valuable inputs for the stages of in vitro tissue development.

PMID: 20815647 [PubMed - indexed for MEDLINE]

   
   
Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing.
January 19, 2011 at 11:17 PM
 

Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing.

Biomaterials. 2010 Dec;31(34):8946-52

Authors: Santoro R, Olivares AL, Brans G, Wirz D, Longinotti C, Lacroix D, Martin I, Wendt D

Apart from partial or total joint replacement, no surgical procedure is currently available to treat large and deep cartilage defects associated with advanced diseases such as osteoarthritis. In this work, we developed a perfusion bioreactor system to engineer human cartilage grafts in a size with clinical relevance for unicompartmental resurfacing of human knee joints (50 mm diameter × 3 mm thick). Computational fluid dynamics models were developed to optimize the flow profile when designing the perfusion chamber. Using the developed system, human chondrocytes could be seeded throughout large 50 mm diameter scaffolds with a uniform distribution. Following two weeks culture, tissues grown in the bioreactor were viable and homogeneously cartilaginous, with biomechanical properties approaching those of native cartilage. In contrast, tissues generated by conventional manual production procedures were highly inhomogeneous and contained large necrotic regions. The unprecedented engineering of human cartilage tissues in this large-scale opens the practical perspective of grafting functional biological substitutes for the clinical treatment for extensive cartilage defects, possibly in combination with surgical or pharmacological therapies to support durability of the implant. Ongoing efforts are aimed at integrating the up-scaled bioreactor based processes within a fully automated and closed manufacturing system for safe, standardized, and GMP compliant production of large-scale cartilage grafts.

PMID: 20800280 [PubMed - indexed for MEDLINE]

   
   
Tissue-engineered conduit using urine-derived stem cells seeded bacterial cellulose polymer in urinary reconstruction and diversion.
January 19, 2011 at 11:17 PM
 

Tissue-engineered conduit using urine-derived stem cells seeded bacterial cellulose polymer in urinary reconstruction and diversion.

Biomaterials. 2010 Dec;31(34):8889-901

Authors: Bodin A, Bharadwaj S, Wu S, Gatenholm P, Atala A, Zhang Y

The objective of this study was to generate bacterial cellulose (BC) scaffolds seeded with human urine-derived stem cells (USC) to form a tissue-engineered conduit for use in urinary diversion. Microporous BC scaffolds were synthesized and USC were induced to differentiate into urothelial and smooth muscle cells (SMC). Induced USC (10(6) cells/cm(2)) were seeded onto BC under static and 3D dynamic (10 or 40 RPM) conditions and cultured for 2 weeks. The urothelial cells and SMC derived from USC formed multilayers on the BC scaffold surface, and some cells infiltrated into the scaffold. The urothelium derived from USC differentiation expressed urothelial markers (uroplakin Ia and AE1/AE3) and the SMC expressed SMC markers (α-smooth muscle actin and desmin). In addition, USC/BC scaffold constructs were implanted into athymic mice, and the cells were tracked using immunohistochemical staining for human nuclear antigen. In vivo, the cells appeared to differentiate and express urothelial and SMC markers. In conclusion, porous BC scaffolds allow 3 dimensional growth of USC, leading to formation of a multilayered urothelium and cell-matrix infiltration. Thus, cell-seeded BC scaffolds hold promise for use in tissue-engineered urinary conduits for urinary reconstruction.

PMID: 20800278 [PubMed - indexed for MEDLINE]

   
   
Tissue engineered human tracheas for in vivo implantation.
January 19, 2011 at 11:17 PM
 

Tissue engineered human tracheas for in vivo implantation.

Biomaterials. 2010 Dec;31(34):8931-8

Authors: Baiguera S, Jungebluth P, Burns A, Mavilia C, Haag J, De Coppi P, Macchiarini P

Two years ago we performed the first clinical successful transplantation of a fully tissue engineered trachea. Despite the clinically positive outcome, the graft production took almost 3 months, a not feasible period of time for patients with the need of an urgent transplantation. We have then improved decellularization process and herein, for the first time, we completely describe and characterize the obtainment of human tracheal bioactive supports. Histological and molecular biology analysis demonstrated that all cellular components and nuclear material were removed and quantitative PCR confirmed it. SEM analysis revealed that the decellularized matrices retained the hierarchical structures of native trachea, and biomechanical tests showed that decellularization approach did not led to any influence on tracheal morphological and mechanical properties. Moreover immunohistological staining showed the preservation of angiogenic factors and angiogenic assays demonstrated that acellular human tracheal scaffolds exert an in vitro chemo-active action and induce strong in vivo angiogenic response (CAM analysis). We are now able to obtained, in a short and clinically useful time (approximately 3 weeks), a bioengineered trachea that is structurally and mechanically similar to native trachea, which exert chemotactive and pro-angiogenic properties and which could be successfully used for clinical tissue engineered airway clinical replacements.

PMID: 20800273 [PubMed - indexed for MEDLINE]

   
   
The effects of processing methods upon mechanical and biologic properties of porcine dermal extracellular matrix scaffolds.
January 19, 2011 at 11:17 PM
 

The effects of processing methods upon mechanical and biologic properties of porcine dermal extracellular matrix scaffolds.

Biomaterials. 2010 Nov;31(33):8626-33

Authors: Reing JE, Brown BN, Daly KA, Freund JM, Gilbert TW, Hsiong SX, Huber A, Kullas KE, Tottey S, Wolf MT, Badylak SF

Biologic materials from various species and tissues are commonly used as surgical meshes or scaffolds for tissue reconstruction. Extracellular matrix (ECM) represents the secreted product of the cells comprising each tissue and organ, and therefore provides a unique biologic material for selected regenerative medicine applications. Minimal disruption of ECM ultrastructure and content during tissue processing is typically desirable. The objective of this study was to systematically evaluate effects of commonly used tissue processing steps upon porcine dermal ECM scaffold composition, mechanical properties, and cytocompatibility. Processing steps evaluated included liming and hot water sanitation, trypsin/SDS/TritonX-100 decellularization, and trypsin/TritonX-100 decellularization. Liming decreased the growth factor and glycosaminoglycan content, the mechanical strength, and the ability of the ECM to support in vitro cell growth (p ≤ 0.05 for all). Hot water sanitation treatment decreased only the growth factor content of the ECM (p ≤ 0.05). Trypsin/SDS/TritonX-100 decellularization decreased the growth factor content and the ability of the ECM to support in vitro cell growth (p ≤ 0.05 for both). Trypsin/Triton X-100 decellularization also decreased the growth factor content of the ECM but increased the ability of the ECM to support in vitro cell growth (p ≤ 0.05 for both). We conclude that processing steps evaluated in the present study affect content, mechanical strength, and/or cytocompatibility of the resultant porcine dermal ECM, and therefore care must be taken in choosing appropriate processing steps to maintain the beneficial effects of ECM in biologic scaffolds.

PMID: 20728934 [PubMed - indexed for MEDLINE]

   
   
CIRM Directors to Hand Out $40 Million Next Week; Meeting Details Not Available to Public
January 19, 2011 at 12:48 PM
 
Directors of the California stem cell agency meet one week from tomorrow to give away $40 million and move forward on electing a new chairman of the $3 billion enterprise come next June.

With six business days left before the meeting, however, few details of what is to be considered are available to the public via the directors' agenda on the CIRM web site. That is in keeping with the agency's
   
   
Ethical care and use of cadavers: A call for a policy.
January 19, 2011 at 11:23 AM
 

Ethical care and use of cadavers: A call for a policy.

Anat Sci Educ. 2011 Jan 17;

Authors: Bernanke DH

PMID: 21243653 [PubMed - as supplied by publisher]

   
   
Suprathel-Antiseptic Matrix: In Vitro Model for Local Antiseptic Treatment?
January 19, 2011 at 11:23 AM
 

Suprathel-Antiseptic Matrix: In Vitro Model for Local Antiseptic Treatment?

Adv Skin Wound Care. 2011 Feb;24(2):64-67

Authors: Ryssel H, Andreas Radu C, Germann G, Kloeters O, Riedel K, Otte M, Kremer T

Acetic acid is a traditional antiseptic agent that has been used for more than 6000 years. The main goal of this study was to demonstrate the suitability of Suprathel (PolyMedics Innovations GmbH, Denkendorf, Germany) in combination with various antiseptic agents to create an "antiseptic-matrix" especially designed for problematic microorganisms such as Proteus vulgaris, Acinetobacter baumannii, or Pseudomonas aeruginosa, which are frequently associated with burns. The study was designed to test the in vitro antimicrobial effect of a "Suprathel-antiseptic matrix" (Suprathel combined with acetic acid 3%, povidone-iodine 11% [Betaisodona], polyhexanide 0.04% [Lavasept], phenoxyethanol 2%/octenidine dihydrochloride 0.1% [Octenisept], mafenide acetate 5%, and chlorhexidine gluconate 1.5%/cetrimid 15% [Hibicet]). As a means to assess the typical bacterial spectrum of a burn unit, the following Gram-negative and Gram-positive bacteria strains were tested: Escherichia coli, P vulgaris, P aeruginosa, A baumannii, Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus, methicillin-resistant S aureus, and β-hemolytic streptococcus groups A and B. The tests showed a positive bactericidal effect of the Suprathel-antiseptic matrix, particularly with problematic Gram-negative bacteria such as P vulgaris, P aeruginosa, and A baumannii, except for the combination of Suprathel and mafenide acetate. It can be concluded that Suprathel-antiseptic matrix appears to be suitable as a local antiseptic agent, but clinical studies need to be performed to confirm these in vitro observations. The authors' previous studies have shown that acetic acid demonstrates a wide antiseptic spectrum for microorganisms typically found in burn patients. The combination of Suprathel and acetic acid worked well in this study and appears to be promising for future clinical application.

PMID: 21242734 [PubMed - as supplied by publisher]

   
   
Lessons from (patho)physiological tissue stiffness and their implications for drug screening, drug delivery and regenerative medicine.
January 19, 2011 at 11:23 AM
 

Lessons from (patho)physiological tissue stiffness and their implications for drug screening, drug delivery and regenerative medicine.

Adv Drug Deliv Rev. 2011 Jan 14;

Authors: Chen WL, Simmons CA

Diseased tissues are noted for their compromised mechanical properties, which contribute to organ failure; regeneration entails restoration of tissue structure and thereby functions. Thus, the physical signature of a tissue is closely associated with its biological function. In this review, we consider a mechanics-centric view of disease and regeneration by drawing parallels between in vivo tissue-level observations and corroborative cellular evidence in vitro to demonstrate the importance of the mechanical stiffness of the extracellular matrix in these processes. This is not intended to devalue the importance of biochemical signalling; in fact, as we discuss, many mechanical stiffness-driven processes not only require cooperation with biochemical cues, but they ultimately converge at common signaling cascades to influence cell and tissue function in an integrative manner. The study of how physical and biochemical signals collectively modulate cell function not only brings forth a more holistic understanding of cell (patho)biology, but it also creates opportunities to control material properties to improve culture platforms for research and drug screening and aid in the rationale design of biomaterials for molecular therapy and tissue engineering applications.

PMID: 21241759 [PubMed - as supplied by publisher]

   
   
Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions - a taskforce report.
January 19, 2011 at 11:23 AM
 

Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions - a taskforce report.

J Oral Rehabil. 2011 Jan 17;

Authors: Svensson P, Baad-Hansen L, Pigg M, List T, Eliav E, Ettlin D, Michelotti A, Tsukiyama Y, Matsuka Y, Jääskeläinen SK, Essick G, Greenspan JD, Drangsholt M

Summary  The goals of an international taskforce on somatosensory testing established by the Special Interest Group of Oro-facial Pain (SIG-OFP) under the International Association for the Study of Pain (IASP) were to (i) review the literature concerning assessment of somatosensory function in the oro-facial region in terms of techniques and test performance, (ii) provide guidelines for comprehensive and screening examination procedures, and (iii) give recommendations for future development of somatosensory testing specifically in the oro-facial region. Numerous qualitative and quantitative psychophysical techniques have been proposed and used in the description of oro-facial somatosensory function. The selection of technique includes time considerations because the most reliable and accurate methods require multiple repetitions of stimuli. Multiple-stimulus modalities (mechanical, thermal, electrical, chemical) have been applied to study oro-facial somatosensory function. A battery of different test stimuli is needed to obtain comprehensive information about the functional integrity of the various types of afferent nerve fibres. Based on the available literature, the German Neuropathic Pain Network test battery appears suitable for the study of somatosensory function within the oro-facial area as it is based on a wide variety of both qualitative and quantitative assessments of all cutaneous somatosensory modalities. Furthermore, these protocols have been thoroughly described and tested on multiple sites including the facial skin and intra-oral mucosa. Standardisation of both comprehensive and screening examination techniques is likely to improve the diagnostic accuracy and facilitate the understanding of neural mechanisms and somatosensory changes in different oro-facial pain conditions and may help to guide management.

PMID: 21241350 [PubMed - as supplied by publisher]

   
   
Nuclear Ago2 regulates ATSCs survival through direct control of miR10b and SEPN1 expression.
January 19, 2011 at 7:01 AM
 

Nuclear Ago2 regulates ATSCs survival through direct control of miR10b and SEPN1 expression.

Aging Cell. 2011 Jan 17;

Authors: Kim BS, Jung JS, Jang JH, Kang KS, Kang SK

Argonaute 2 (Ago2) has a leading function in miRNA-induced RNA silencing, a conserved gene regulatory mechanism in cells and organisms. miRNAs are critical for stem cell self-renewal, development and other functions. Here, we report that nuclear Ago2, by binding to a specific region of functional genes, directly controls adipose tissue-derived stem cell (ATSC) survival in response to a critical dose of reactive oxygen species (ROS)-mediated oxidative cell damage or senescence. The role of nuclear Ago2 has not been previously reported. Here, we show that human ATSCs in which Ago2 was downregulated underwent apoptosis. Silencing of Ago2 in ATSCs significantly induces upregulation of miR10b and miR23b expression. These miRNAs directly interfere with ROS scavenging gene expression, such as TXNL1 and GPX3. Upregulation of miR10b and miR23b is sufficient to induce ATSC cell apoptosis via p38 MAPK phosphorylation and caspase 3 activation. In addition, Ago2 overexpression or interference by miR10b and miR23b expression in ATSCs partially rescued H(2) O(2) /ROS-mediated apoptotic cell death by upregulating the expression of TXNL2, JUNK, caspase-3, and cytochrome C. Nuclear Ago2-mediated miR10b and miR23b downregulation also allows cells to escape senescence, which results in TERT activation, stemness overexpression, and improved self-renewal and differentiation through Wnt5a/β-catenin activation. Ago2 expression is critical for stem cells to escape senescence by downregulating miR10b and miR23b. The Ago2-binding gene selenoprotein N1 (SEPN1) was also effectively involved in ATSC survival and self-renewal through ROS-mediated p38 MAPK inactivation.

PMID: 21241449 [PubMed - as supplied by publisher]

   
   
Preservation of the cardiac function in infarcted rat hearts by the transplantation of adipose-derived stem cells with injectable fibrin scaffolds.
January 19, 2011 at 7:01 AM
 

Preservation of the cardiac function in infarcted rat hearts by the transplantation of adipose-derived stem cells with injectable fibrin scaffolds.

Exp Biol Med (Maywood). 2010 Dec;235(12):1505-15

Authors: Zhang X, Wang H, Ma X, Adila A, Wang B, Liu F, Chen B, Wang C, Ma Y

Cell-based therapy can improve cardiac function but is limited by the low cell retention and survival within ischemic tissues. Injectable cardiac tissue engineering aims to support cell-based therapies and enhance their efficacy for cardiac diseases. So far, no research has been devoted to studying the usefulness of the combination of fibrin glue (as scaffold) and adipose-derived stem cells (ADSCs) to treat myocardial infarction. In our study, the rat ADSCs were isolated from subcutaneous adipose tissues. The surface phenotype of these cells was analyzed by flow cytometry. The fibrin glue was then co-injected with ADSCs into the left ventricular wall of rat infarction models. The structure and functional consequences of transplantation were determined by detailed histological analysis and echocardiography. Most cultured ADSCs expressed CD105 and CD90, and were negative for CD34 and CD45. After injection, both the 24-h cell retention and four-week graft size were significantly higher and larger in the Fibrin + ADSCs group than those of the ADSCs group alone (P < 0.01). The heart function improved significantly in the Fibrin + ADSCs group compared with that of the ADSCs group four weeks after transplantation (P < 0.01). In addition, the arteriole densities within the infarcted area improved significantly in the Fibrin + ADSCs group compared with those in the ADSCs group four weeks after transplantation (P < 0.01). In conclusion, the ADSCs with the fibrin glue has the therapeutic potential to improve the function of infarcted hearts. The method of in situ injectable tissue engineering combining fibrin glue with ADSCs is promising clinically.

PMID: 21127347 [PubMed - indexed for MEDLINE]

   
     
 
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