|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | From Bone to Brain: Human Skeletal Stem Cell Therapy for Stroke. Cent Nerv Syst Agents Med Chem. 2011 Apr 27; Authors: Zhou S Human adult skeletal stem cells, a.k.a. mesenchymal stem cells or marrow stromal cells (MSCs), have been identified as precursors of several different mesenchymal cellular lineages, including osteoblasts, chondrocytes, myoblasts, adipocytes, and fibroblasts, as well as non-mesenchymal lineages including neurons and glial cells. Adult stem cell transplantation is a promising strategy for the treatment of stroke. MSCs are also used as a platform for gene therapies and therapeutic agents. In this review, we discuss recent progress of human skeletal stem cell biology, in vitro differentiation of MSCs into neural stem cells and neurons, MSC therapy for stroke, MSC aging and the challenge of autologous cell therapy for stroke in elderly patients. PMID: 21521166 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Shortcuts to making cardiomyocytes. Nat Cell Biol. 2011 Mar;13(3):191-3 Authors: Xu H, Yi BA, Chien KR The adult human heart lacks sufficient regenerative capacity to recover after a myocardial infarction. Cell-based therapy has emerged as a potential treatment for the failing heart; however, a key issue for the success of future cell-based therapies is the ability to obtain patient-specific high-quality cardiomyocytes in a fast and efficient manner. Recent progress has been made towards this goal using reprogramming-based approaches. PMID: 21364566 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A chromatographically purified human TGF-β1 fraction from virally inactivated platelet lysates. Vox Sang. 2011 Apr 26; Authors: Burnouf T, Chang CW, Kuo YP, Wu YW, Tseng YH, Su CY Background and Objectives TGF-β1 exerts important physiological functions in osteogenesis and chondrogenesis and may be of therapeutic interest. The aim of this work was to develop a scalable purification process of TGF-β1 from virally inactivated human platelets. Study Design and Methods Apheresis platelet concentrates (N = 12) were solvent/detergent (S/D) treated (1% TnBP/1% Triton X-45; 31 °C) and the resulting platelet lysates were clarified by oil extraction and centrifugation, then chromatographed on an anion-exchange DEAE-Sepharose Fast-Flow column equilibrated in a PBS buffer, pH 7·5. The column was washed to eliminate unbound proteins and the S/D agents. Bound proteins were eluted using a 1 M NaCl-PBS buffer pH 7·5 (DEAE-eluate). The content in TGF-β1, PDGF-AB, VEGF, IGF-1, EGF, and b-FGF was measured by ELISA. Proteins, lipids, and S/D agents were assessed. Protein profile was determined by SDS-PAGE under reduced or non-reduced conditions. Results Most proteins, including albumin and immunoglobulins G, A, and M did not bind to the DEAE column as evidenced also by SDS-PAGE. Essentially all PDGF, VEGF, and IGF were in the breakthrough. The DEAE-eluate contained close to 60% of the TGF-β1 at a mean concentration of about 102 ng/ml, whereas EGF, b-FGF were at about 0·72 and 0·18 ng/ml, respectively. The content in TnBP and Triton X-45 was <2 ppm. Conclusion A fraction enriched in TGF-β1 can be prepared from virally inactivated human platelet lysates using an easily scale process. Its interest in regenerative medicine and cell therapy will be evaluated in further studies. PMID: 21521235 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | TIMP-1 deficiency subverts cell cycle dynamics in murine long-term HSCs. Blood. 2011 Apr 26; Authors: Rossi L, Ergen AV, Goodell MA In addition to the well-recognized role in extracellular matrix remodeling, the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) has been suggested to be involved in the regulation of numerous biological functions, including cell proliferation and survival. We therefore hypothesized that TIMP-1 might be involved in the homeostatic regulation of hematopoietic stem cells (HSCs), whose biological behavior is the synthesis of both microenvironmental and intrinsic cues. We found that TIMP-1(-/-) mice have decreased BM cellularity and, consistent with this finding, TIMP-1(-/-) HSCs display reduced capability of long-term repopulation. Interestingly, the cell cycle distribution of TIMP-1(-/-) stem cells appears distorted, with a dysregulation at the level of the G(1) phase. TIMP-1(-/-) HSCs also display increased levels of p57, p21, and p53, suggesting that TIMP-1 could be intrinsically involved in the regulation of HSC cycling dynamics. Of note, TIMP-1(-/-) HSCs present decreased levels of CD44 glycoprotein, whose expression has been proven to be controlled by p53, the master regulator of the G(1)/S transition. Our findings establish a role for TIMP-1 in regulating HSC function, suggesting a novel mechanism presiding over stem cell quiescence in the framework of the BM milieu. PMID: 21521782 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biochip∕laser cell deposition system to assess polarized axonal growth from single neurons and neuron∕glia pairs in microchannels with novel asymmetrical geometries. Biomicrofluidics. 2011;5(1):13408 Authors: Pirlo RK, Sweeney AJ, Ringeisen BR, Kindy M, Gao BZ Axon path-finding plays an important role in normal and pathogenic brain development as well as in neurological regenerative medicine. In both scenarios, axonal growth is influenced by the microenvironment including the soluble molecules and contact-mediated signaling from guiding cells and cellular matrix. Microfluidic devices are a powerful tool for creating a microenvironment at the single cell level. In this paper, an asymmetrical-channel-based biochip, which can be later incorporated into microfluidic devices for neuronal network study, was developed to investigate geometric as well as supporting cell control of polarized axonal growth in forming a defined neuronal circuitry. A laser cell deposition system was used to place single cells, including neuron-glia pairs, into specific microwells of the device, enabling axonal growth without the influence of cytophilic∕phobic surface patterns. Phase microscopy showed that a novel "snag" channel structure influenced axonal growth in the intended direction 4:1 over the opposite direction. In heterotypic experiments, glial cell influence over the axonal growth path was observed with time-lapse microscopy. Thus, it is shown that single cell and heterotypic neuronal path-finding models can be developed in laser patterned biochips. PMID: 21522498 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Electrospinning jets and nanofibrous structures. Biomicrofluidics. 2011;5(1):13403 Authors: Garg K, Bowlin GL Electrospinning is a process that creates nanofibers through an electrically charged jet of polymer solution or melt. This technique is applicable to virtually every soluble or fusible polymer and is capable of spinning fibers in a variety of shapes and sizes with a wide range of properties to be used in a broad range of biomedical and industrial applications. Electrospinning requires a very simple and economical setup but is an intricate process that depends on several molecular, processing, and technical parameters. This article reviews information on the three stages of the electrospinning process (i.e., jet initiation, elongation, and solidification). Some of the unique properties of the electrospun structures have also been highlighted. This article also illustrates some recent innovations to modify the electrospinning process. The use of electrospun scaffolds in the field of tissue engineering and regenerative medicine has also been described. PMID: 21522493 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cardiac muscle regeneration: lessons from development. Genes Dev. 2011 Feb 15;25(4):299-309 Authors: Mercola M, Ruiz-Lozano P, Schneider MD The adult human heart is an ideal target for regenerative intervention since it does not functionally restore itself after injury yet has a modest regenerative capacity that could be enhanced by innovative therapies. Adult cardiac cells with regenerative potential share gene expression signatures with early fetal progenitors that give rise to multiple cardiac cell types, suggesting that the evolutionarily conserved regulatory networks that drive embryonic heart development might also control aspects of regeneration. Here we discuss commonalities of development and regeneration, and the application of the rich developmental biology heritage to achieve therapeutic regeneration of the human heart. PMID: 21325131 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Preface to Special Topic: Biological microfluidics in tissue engineering and regenerative medicine. Biomicrofluidics. 2011;5(1):13301 Authors: Jayasinghe SN In this special issue of Biomicrofluidics, many manifestations of biological microfluidics have been highlighted that have significance to regenerative biology and medicine. The collated articles demonstrate the applicability of these biological microfluidics for studying a wide range of biomedical problems most useful for understanding and shining light on basic biology to those applications relevant to clinical medicine. PMID: 21522490 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Preface to Special Topic: Biological microfluidics in tissue engineering and regenerative medicine. Biomicrofluidics. 2011;5(1):13301 Authors: Jayasinghe SN In this special issue of Biomicrofluidics, many manifestations of biological microfluidics have been highlighted that have significance to regenerative biology and medicine. The collated articles demonstrate the applicability of these biological microfluidics for studying a wide range of biomedical problems most useful for understanding and shining light on basic biology to those applications relevant to clinical medicine. PMID: 21522490 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Bone tissue: hierarchical simulations for clinical applications. J Biomech. 2011 Jan 11;44(2):211-2 Authors: Ascenzi MG, Reilly GC PMID: 21051041 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of bone scaffolds by micro-CT. Osteoporos Int. 2011 Apr 27; Authors: Peyrin F This paper reviews the possibilities offered by X-ray micro-CT in bone tissue engineering. This technique provides a fast, nondestructive, and 3D quantification of bone scaffolds, bone ingrowth, and microvascularization. Synchrotron radiation absorption and phase micro-CT offer additional advantages to image newly formed bone in bioceramic scaffolds and pre-bone matrix. PMID: 21523402 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Acellular dermal matrix seeded with autologous fibroblasts improves wound breaking strength in a rodent soft tissue damage model in neoadjuvant settings. J Biomater Appl. 2011 Jan;25(5):413-27 Authors: Roessner ED, Thier S, Hohenberger P, Schwarz M, Pott P, Dinter D, Smith M Soft tissue defects following resectional surgery or trauma often result in deadspaces and require free or pedicled flaps. A programmed formation of filling tissue with enhanced biomechanical properties could be helpful. This study examined the effects on wound healing of acellular dermal matrix (ADM) seeded with autologous fibroblasts in a standardized rodent model. As pre- or postoperative radiotherapy is standard in many treatments of malignancies, we also investigated the effects of additional radiotherapy. Fischer rats were randomised and received a standardized unilateral soft tissue defect at the buttock. The defect was filled with ADM+fibroblasts or ADM alone. Controls received no filling. Either no radiation, adjuvant (postoperative) or neoadjuvant (preoperative) radiation was applied to the defect site. Six weeks later the defect volume was measured by MR-tomography. Wound breaking strength was examined by tensiometry according to German Industrial Standards. Filling of the defect side was significantly larger in ADM and ADM+fibroblast treated groups compared to the control group in all settings. Wound breaking strength in the unimodal setting was significantly improved in the ADM+fibroblasts group compared to the ADM group. In the neoadjuvant setting there was no significant difference between control and ADM group. However, the ADM+fibroblasts groups showed a significantly increased wound breaking strength compared to the control and the ADM-alone group. Seeded or unseeded ADM is able to fill deadspace in this rodent model in all settings. Implanting non-irradiated, vital, proliferating autologous fibroblasts on ADM results in significantly increased wound breaking strength. PMID: 20042428 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Top down and bottom up engineering of bone. J Biomech. 2011 Jan 11;44(2):304-12 Authors: Knothe Tate ML The goal of this retrospective article is to place the body of my lab's multiscale mechanobiology work in context of top-down and bottom-up engineering of bone. We have used biosystems engineering, computational modeling and novel experimental approaches to understand bone physiology, in health and disease, and across time (in utero, postnatal growth, maturity, aging and death, as well as evolution) and length scales (a single bone like a femur, m; a sample of bone tissue, mm-cm; a cell and its local environment, μm; down to the length scale of the cell's own skeleton, the cytoskeleton, nm). First we introduce the concept of flow in bone and the three calibers of porosity through which fluid flows. Then we describe, in the context of organ-tissue, tissue-cell and cell-molecule length scales, both multiscale computational models and experimental methods to predict flow in bone and to understand the flow of fluid as a means to deliver chemical and mechanical cues in bone. Addressing a number of studies in the context of multiple length and time scales, the importance of appropriate boundary conditions, site specific material parameters, permeability measures and even micro-nanoanatomically correct geometries are discussed in context of model predictions and their value for understanding multiscale mechanobiology of bone. Insights from these multiscale computational modeling and experimental methods are providing us with a means to predict, engineer and manufacture bone tissue in the laboratory and in the human body. PMID: 21146825 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Biomimetic micro∕nanostructured functional surfaces for microfluidic and tissue engineering applications. Biomicrofluidics. 2011;5(1):13411 Authors: Stratakis E, Ranella A, Fotakis C This paper reviews our work on the application of ultrafast pulsed laser micro∕nanoprocessing for the three-dimensional (3D) biomimetic modification of materials surfaces. It is shown that the artificial surfaces obtained by femtosecond-laser processing of Si in reactive gas atmosphere exhibit roughness at both micro- and nanoscales that mimics the hierarchical morphology of natural surfaces. Along with the spatial control of the topology, defining surface chemistry provides materials exhibiting notable wetting characteristics which are potentially useful for open microfluidic applications. Depending on the functional coating deposited on the laser patterned 3D structures, we can achieve artificial surfaces that are (a) of extremely low surface energy, thus water-repellent and self-cleaned, and (b) responsive, i.e., showing the ability to change their surface energy in response to different external stimuli such as light, electric field, and pH. Moreover, the behavior of different kinds of cells cultured on laser engineered substrates of various wettabilities was investigated. Experiments showed that it is possible to preferentially tune cell adhesion and growth through choosing proper combinations of surface topography and chemistry. It is concluded that the laser textured 3D micro∕nano-Si surfaces with controllability of roughness ratio and surface chemistry can advantageously serve as a novel means to elucidate the 3D cell-scaffold interactions for tissue engineering applications. PMID: 21522501 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro concurrent endothelial and osteogenic commitment of adipose-derived stem cells and their genomical analyses through CGH array: novel strategies to increase the successful engraftment of a tissue engineered bone grafts. Stem Cells Dev. 2011 Apr 26; Authors: Gardin C, Bressan E, Ferroni L, Nalesso E, Vindigni V, Stellni E, Pinton P, Sivolella S, Zavan B In the field of tissue engineering, adult stem cells are increasingly recognized as an important tool for in vitro reconstructed tissue-engineered grafts. In the world of cell therapies, mesenchymal stem cells from bone marrow or adipose tissue are undoubtedly the most promising progenitors for tissue engineering applications. In this setting, adipose-derived stem cells (ADSC) are generally similar to those derived from bone marrow and are most conveniently extracted from tissue removed in elective cosmetic liposuction procedures; they also show a great potential for endothelization. The aim of the present work was to investigate how the co-commitment into a vascular and bone phenotype of ADSC could be a usefull tools for improving the in vitro and in vivo reconstruction of a vascularized bone graft. Human ADSC obtained from abdominoplasty procedures were loaded in a hydroxyapatite clinical-grade scaffold, co-differentiated and tested for proliferation, cell distribution, and osteogenic and vasculogenic gene expression. The chromosomal stability of the cultures was investigated using the CGH array for 3D cultures. ADSC adhesion, distribution, proliferation and gene expression not only demonstrated a full osteogenic and vasculogenic commitment in vitro and in vivo, but also showed that endothelization strongly improves their osteogenic commitment. In the end, genetic analyses confirmed that no genomical alteration in long-term in vitro culture of ADSC in 3D scaffolds occurs. PMID: 21521013 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Multiscale modeling of bone tissue with surface and permeability control. J Biomech. 2011 Jan 11;44(2):321-9 Authors: Gonçalves Coelho P, Rui Fernandes P, Carriço Rodrigues H Natural biological materials usually present a hierarchical arrangement with various structural levels. The biomechanical behavior of the complex hierarchical structure of bone is investigated with models that address the various levels corresponding to different scales. Models that simulate the bone remodeling process concurrently at different scales are in development. We present a multiscale model for bone tissue adaptation that considers the two top levels, whole bone and trabecular architecture. The bone density distribution is calculated at the macroscale (whole bone) level, and the trabecular structure at the microscale level takes into account its mechanical properties as well as surface density and permeability. The bone remodeling process is thus formulated as a material distribution problem at both scales. At the local level, the biologically driven information of surface density and permeability characterizes the trabecular structure. The model is tested by a three-dimensional simulation of bone tissue adaptation for the human femur. The density distribution of the model shows good agreement with the actual bone density distribution. Permeability at the microstructural level assures interconnectivity of pores, which mimics the interconnectivity of trabecular bone essential for vascularization and transport of nutrients. The importance of this multiscale model relays on the flexibility to control the morphometric parameters that characterize the trabecular structure. Therefore, the presented model can be a valuable tool to define bone quality, to assist with diagnosis of osteoporosis, and to support the development of bone substitutes. PMID: 21036359 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cell-enclosing gelatin-based microcapsule production for tissue engineering using a microfluidic flow-focusing system. Biomicrofluidics. 2011;5(1):13402 Authors: Sakai S, Ito S, Inagaki H, Hirose K, Matsuyama T, Taya M, Kawakami K Gelatin-based microcapsule production using a microfluidic system and the feasibility of the resultant microcapsules for constructing spherical tissues surrounded by heterogeneous cells were studied. The first cell-encapsulation and subsequent cell-enclosing microparticle encapsulation were achieved using a microfluidic flow-focusing droplet production system. A hollow-core structure of about 150 μm in diameter was developed by incubating the resultant microparticles at 37 °C, which induced thermal melting of the enclosed unmodified gelatin microparticles. Mammalian cells filled the hollow-cores after 4 days of incubation. A cell layer on the cell-enclosing microcapsules was developed by simply suspending the microcapsules in medium containing adherent fibroblast cells. This method may prove useful for the generation of gelatin microcapsules using a microfluidic system for formation of artificial tissue constructs. PMID: 21522492 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Biomechanics and tissue engineering. Osteoporos Int. 2011 Apr 27; Authors: Pioletti DP Development of artificial scaffold for musculo-skeletal applications, especially in load-bearing situations, requires the consideration of biomechanical aspects for its integrity and its function. However, the biomechanical loading could also be used to favour tissue formation through mechano-transduction phenomena. Design of scaffold could take advantages of this intrinsic mechanical loading. PMID: 21523395 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Electrospinning jets and nanofibrous structures. Biomicrofluidics. 2011;5(1):13403 Authors: Garg K, Bowlin GL Electrospinning is a process that creates nanofibers through an electrically charged jet of polymer solution or melt. This technique is applicable to virtually every soluble or fusible polymer and is capable of spinning fibers in a variety of shapes and sizes with a wide range of properties to be used in a broad range of biomedical and industrial applications. Electrospinning requires a very simple and economical setup but is an intricate process that depends on several molecular, processing, and technical parameters. This article reviews information on the three stages of the electrospinning process (i.e., jet initiation, elongation, and solidification). Some of the unique properties of the electrospun structures have also been highlighted. This article also illustrates some recent innovations to modify the electrospinning process. The use of electrospun scaffolds in the field of tissue engineering and regenerative medicine has also been described. PMID: 21522493 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Challenges and Opportunities in the Management of the Aging Voice. Otolaryngol Head Neck Surg. 2011 Apr 26; Authors: Johns MM, Arviso LC, Ramadan F Presbyphonia, or age-related dysphonia, is a diagnosis of exclusion, and other comorbidities must be considered in a complete evaluation of elderly patients with dysphonia. The aging voice can have a significant effect on the quality of life of the patient. In addition to the molecular effects of aging on the laryngeal tissues, the etiology of presbyphonia is often multifactorial because of comorbidities in the other organ systems involved in phonation. After a comprehensive evaluation, presbyphonia may be treated conservatively with voice therapy or with a range of interventions. Research into tissue engineering and electrical reanimation offers future options for treatment of presbyphonia. Currently, a multidisciplinary approach offers the most complete improvement in the vocal quality of life in this patient population. PMID: 21521897 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Microfluidic devices for studying heterotypic cell-cell interactions and tissue specimen cultures under controlled microenvironments. Biomicrofluidics. 2011;5(1):13406 Authors: Zervantonakis IK, Kothapalli CR, Chung S, Sudo R, Kamm RD Microfluidic devices allow for precise control of the cellular and noncellular microenvironment at physiologically relevant length- and time-scales. These devices have been shown to mimic the complex in vivo microenvironment better than conventional in vitro assays, and allow real-time monitoring of homotypic or heterotypic cellular interactions. Microfluidic culture platforms enable new assay designs for culturing multiple different cell populations and∕or tissue specimens under controlled user-defined conditions. Applications include fundamental studies of cell population behaviors, high-throughput drug screening, and tissue engineering. In this review, we summarize recent developments in this field along with studies of heterotypic cell-cell interactions and tissue specimen culture in microfluidic devices from our own laboratory. PMID: 21522496 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Aqueous biphasic microprinting approach to tissue engineering. Biomicrofluidics. 2011;5(1):13404 Authors: Tavana H, Takayama S We summarize a recently developed microtechnology for printing biomaterials on biological surfaces. The technique is based on the use of immiscible aqueous solutions of two biopolymers and allows spatially defined placement of cells and biomolecules suspended in the denser aqueous phase on existing cell layers and extracellular matrix hydrogel surfaces maintained in the second phase. Printing takes place due to an extremely small interfacial tension and density difference between the two aqueous phases. The contact-free printing process ensures that both printed cells and the underlying cell monolayer maintain full viability and functionality. The technique accommodates both arbitrarily shaped patterns and microarrays of cells and bioreagents. The capability to print cells and small molecules on existing cell layers enables unique interrogations of the effects of cell-cell and cell-material interaction on cell fate and function. Furthermore, the very gentle conditions and the ability to directly pattern nongel embedded cells over cells make this technology appealing to tissue engineering applications where patterned multicellar organization with minimal scaffolding materials is needed, such as in dense tissues of the skeletal muscle and liver. PMID: 21522494 [PubMed - in process] | | | | | | | | | |  | |  | |  |
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