|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Stem cell therapy for cardiovascular diseases: are we still at the beginning of a long road? Cardiovasc Hematol Disord Drug Targets. 2010 Sep 1;10(3):158-60 Authors: Gonçalves LM PMID: 21247407 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Labeling of Luciferase/eGFP-Expressing Bone Marrow-Derived Stromal Cells with Fluorescent Micron-Sized Iron Oxide Particles Improves Quantitative and Qualitative Multimodal Imaging of Cellular Grafts In Vivo. Mol Imaging Biol. 2011 Jan 19; Authors: De Vocht N, Bergwerf I, Vanhoutte G, Daans J, De Visscher G, Chatterjee S, Pauwels P, Berneman Z, Ponsaerts P, Van der Linden A PURPOSE: Development of multimodal imaging strategies is currently of utmost importance for the validation of preclinical stem cell therapy studies. PROCEDURES: We performed a combined labeling strategy for bone marrow-derived stromal cells (BMSC) based on genetic modification with the reporter genes Luciferase and eGFP (BMSC-Luc/eGFP) and physical labeling with blue fluorescent micron-sized iron oxide particles (MPIO) in order to unambiguously identify BMSC localization, survival, and differentiation following engraftment in the central nervous system of mice by in vivo bioluminescence (BLI) and magnetic resonance imaging and postmortem histological analysis. RESULTS: Using this combination, a significant increase of in vivo BLI signal was observed for MPIO-labeled BMSC-Luc/eGFP. Moreover, MPIO labeling of BMSC-Luc/eGFP allows for the improved identification of implanted cells within host tissue during histological observation. CONCLUSIONS: This study describes an optimized labeling strategy for multimodal stem cell imaging resulting in improved quantitative and qualitative detection of cellular grafts. PMID: 21246293 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human Umbilical Cord-Derived Schwann-Like Cell Transplantation Combined with Neurotrophin-3 Administration in Dyskinesia of Rats with Spinal Cord Injury. Neurochem Res. 2011 Jan 18; Authors: Yan-Wu G, Yi-Quan K, Ming L, Ying-Qian C, Xiao-Dan J, Shi-Zhong Z, Wang-Ming Z, Chuan-Zhi D Mesenchymal stem cells are capable of differentiating into Schwann-like cells. In this study, we induced human umbilical-cord mesenchymal stem cells (HUMSCs) in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with Schwann-like cells. These HUMSC-derived Schwann-like cells, after grafting into the injured area of the rats' spinal cord injury (SCI), showed a partial therapeutic effect in terms of improving the motor function. Neurotrophin-3 (NT-3) was reported to improve the local microenvironment of the grafted cells, and we, therefore, further tested the effect of Schwann-like cell grafting combined with NT-3 administration at the site of cell transplantation. The results showed that NT-3 administration significantly promoted the survival of the grafted cells in the host-injured area. Significant improvement in rats treated by Schwann-like cell grafting combined with NT-3 administration was demonstrated in the behavioral test as compared with that in animal models received the cell grafting only. These results suggest that transplantation of the Schwann-like cells combined with NT-3 administration may represent a new strategy of stem cell therapy for spinal cord injury. PMID: 21243429 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | Combination stem cell therapy for the treatment of medically refractory coronary ischemia: a Phase I study. Cardiovasc Revasc Med. 2011 Jan-Mar;12(1):29-34 Authors: Lasala GP, Silva JA, Kusnick BA, Minguell JJ Infusion of a source of endothelial progenitor cells (EPC) into the ischemic myocardium is emerging as a promising therapy for coronary ischemia, probably mediated by the formation of new blood vessels. Studies have shown that while the procedure is safe and feasible, efficacy results are contentious. The investigators hypothesized that the infusion of a combination cell product consisting of a source of EPC and mesenchymal stem cells (MSC) is safe and promotes the formation of more stable and mature blood vessels resulting in improved clinical outcomes. PMID: 21241969 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells in clinical practice: applications and warnings. J Exp Clin Cancer Res. 2011 Jan 17;30(1):9 Authors: Lodi D, Iannitti T, Palmieri B ABSTRACT: Stem cells are a relevant source of information about cellular differentiation, molecular processes and tissue homeostasis, but also one of the most putative biological tools to treat degenerative diseases. This review focuses on human stem cells clinical and experimental application. Our aim is to take a correct view of the available stem cell subtypes and their rational use in the medical area, with a specific focus on their therapeutic benefits and side effects. We have reviewed the main clinical trials dividing them basing on their clinical applications, and taking into account the ethical issue associated with the stem cell therapy. PMID: 21241480 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem Cell Therapy for the Bladder: Where Do We Stand? J Urol. 2011 Jan 14; Authors: Lin CS PMID: 21239018 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Enhancement of wound healing by secretory factors of endothelial precursor cells derived from human embryonic stem cells. Cytotherapy. 2011 Feb;13(2):165-78 Authors: Lee MJ, Kim J, Lee KI, Shin JM, Chae JI, Chung HM Abstract Background aims. Stem cells have been shown to have a therapeutic effect in several ischemic animal models, including hindlimb ischemia and chronic wound. We examined the wound-healing effect of secretory factors released by human embryonic stem cell (hESC)-derived endothelial precursor cells (EPC) in cutaneous excisional wound models. Methods. hESC-EPC were sorted by CD133/KDR, and endothelial characteristics were confirmed by reverse transcription (RT)-polymerase chain reaction (PCR), Matrigel assay and ac-LDL uptake. Conditioned medium (CM) of hESC-EPC was prepared, and concentrated hESC-EPC CM was applied in a mouse excisional wound model. Results. hESC-EPC CM accelerated wound healing and increased the tensile strength of wounds after topical treatment and subcutaneous injection. In addition, hESC-EPC CM treatment caused more rapid re-formation of granulation tissue and re-epithelialization of wounds compared with control vehicle medium and CB-EPC CM-treated wounds. In vitro, hESC-EPC CM significantly improved the proliferation and migration of dermal fibroblasts and epidermal keratinocytes. hESC-EPC CM also increased the extracellular matrix synthesis of fibroblasts. Analysis of hESC-EPC CM with a multiplex cytokine array system indicated that hESC-EPC secreted distinctively different cytokines and chemokines, such as epidermal growth factor (EGF), fibroblast growth factor (bFGF), fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor (VEGF), which are well known to be important in normal angiogenesis and wound healing. Conclusions. This study has demonstrated the wound-healing effect of hESC-EPC CM and characterized the spectrum of cytokines released by hESC-EPC that are functionally involved in the wound-healing process. These results suggest that secretory factors released from stem cells could be an important mediator of stem cell therapy in ischemic tissue diseases. PMID: 21235296 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Reconstruction of rat calvarial defects with human mesenchymal stem cells and osteoblast-like cells in poly-lactic-co-glycolic acid scaffolds. Eur Cell Mater. 2010;20:109-20 Authors: Zong C, Xue D, Yuan W, Wang W, Shen D, Tong X, Shi D, Liu L, Zheng Q, Gao C, Wang J Human mesenchymal stem cells (hMSCs) can be used for xenogenic transplantation due to their low immunogenicity, high proliferation rate, and multi-differentiation potentials. Therefore, hMSCs are an ideal seeding source for tissue engineering. The present study evaluates the reconstruction effects of hMSCs and osteoblast-like cells differentiated from hMSCs in poly-lactic-co-glycolic acid (PLGA) scaffolds on the calvarial defect of rats. Two bilateral full-thickness defects (5mm in diameter) were created in the calvarium of nonimmunosuppressed Sprague-Dawley rats. The defects were filled by PLGA scaffolds with hMSCs (hMSC Construct) or with osteoblast-like cells differentiated from hMSCs (Osteoblast Construct). The defects without any graft (Blank Defect) or filled with PLGA scaffold without any cells (Blank Scaffold) were used as controls. Evaluation was performed using macroscopic view, histology and immunohistochemical analysis respectively at 10 and 20 weeks after transplantation. In addition, fluorescent carbocyanine CM-Dil was used to track the implanted cells in vivo during transplantation. The results showed that while both hMSC Construct and Osteoblast Construct led to an effective reconstruction of critical-size calvarial defects, the bone reconstruction potential of hMSC Construct was superior to that of Osteoblast Construct in non-autogenous applications. Our findings verify the feasibility of the use of xenogenic MSCs for tissue engineering and demonstrate that undifferentiated hMSCs are more suitable for bone reconstruction in xenotransplantation models. PMID: 21249628 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Multifactorial optimization of endothelial cell growth using modular synthetic extracellular matrices. Integr Biol (Camb). 2011 Jan 19; Authors: Jung JP, Moyano JV, Collier JH Extracellular matrices (ECMs) are complex materials, containing at least dozens of different macromolecules that are assembled together, thus complicating their optimization towards applications in 3D cell culture or tissue engineering. The natural complexity of ECMs has limited cell-matrix investigations predominantly to experiments where only one matrix component is adjusted at a time, making it difficult to uncover interactions between different matrix components or to efficiently determine optimal matrix compositions for specific desired biological responses. Here we have developed modular synthetic ECMs based on peptide self-assembly whose incorporation of multiple different peptide ligands can be adjusted. The peptides can co-assemble in a wide range of combinations to form hydrogels of uniform morphology and consistent mechanical properties, but with precisely varied mixtures of peptide ligands. The modularity of this system in turn enabled multi-factorial experimental designs for investigating interactions between these ligands and for determining a multi-peptide matrix formulation that maximized endothelial cell growth. In cultures of HUVECs, we observed a previously unknown antagonistic interaction between the laminin-derived peptide YIGSR and RGDS-mediated cell attachment and growth. We also identified an optimized combination of self-assembled peptides bearing the ligands RGDS and IKVAV that led to endothelial cell growth equivalent to that on native full-length fibronectin. Both of these findings would have been challenging to uncover using more traditional one-factor-at-a-time analyses. PMID: 21249249 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioreactors in tissue engineering. Technol Health Care. 2011 Jan 1;19(1):55-69 Authors: Plunkett N, O'Brien FJ A bioreactor can be defined as a device that uses mechanical means to influence biological processes. In tissue engineering bioreactors can be used to aid in the in vitro development of new tissue by providing biochemical and physical regulatory signals to cells and encouraging them to undergo differentiation and/or to produce extracellular matrix prior to in vivo implantation. This chapter discusses the necessity for bioreactors in tissue engineering, the numerous types of bioreactor that exist, the means by which they stimulate cells and how their functionality is governed by the requirements of the specific tissue being engineered and the cell type undergoing stimulation. PMID: 21248413 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Dynamic Tensile Loading Improves the Functional Properties of MSC-Laden Nanofiber-Based Fibrocartilage. Tissue Eng Part A. 2011 Jan 19; Authors: Baker BM, Shah RP, Huang AH, Mauck RL Fibrocartilaginous tissues such as the meniscus serve critical load-bearing roles, relying on arrays of collagen fibers to resist tensile loads experienced with normal activity. As these structures are often injured and possess limited healing capacity, there exists great demand for tissue engineered replacements. Towards recreating the structural features of these anisotropic tissues in vitro, we employ scaffolds composed of co-aligned, polymer nanofibers that direct mesenchymal stem cell (MSC) orientation and the formation of organized extracellular matrix (ECM). Concomitant with ECM synthesis, the mechanical properties of constructs increase with long-term free-swelling culture, but ultimately failed to achieve equivalence with meniscal fibrocartilage. As mechanical forces are essential to the development and maintenance of musculoskeletal tissues, this work examined the effect of cyclic tensile loading on MSC-laden nanofibrous constructs. We hypothesized that this loading modality would modulate the transcriptional behavior of seeded MSCs, spur the deposition of additional extracellular matrix, and lead to enhancements in construct mechanical properties compared to free-swelling controls. Fiber-aligned scaffolds were seeded with MSCs and dynamically loaded daily in tension or maintained as nonloaded controls for 4 weeks. With mechanical stimulation, fibrous gene expression increased and more collagen content was deposited relative to nonloaded controls. These changes resulted in a 16% increase in tensile modulus over this period. These results show that dynamic tensile loading enhances the maturation of MSC-laden aligned nanofibrous constructs, suggesting that recapitulation of the structural and mechanical environment of load-bearing tissues results in increases in functional properties which can be exploited for tissue engineering applications. PMID: 21247342 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In Vitro Assessment of the Differentiation Potential of BMSCs on Genipin-chitosan Conjugation Scaffold with Surface Hydroxyapatite Nanostructure for Bone Tissue Engineering. Tissue Eng Part A. 2011 Jan 19; Authors: Wang G, Zheng L, Zhao H, Miao J, Sun C, Ren N, Liu H, Wang J, Tao X Increasing evidence has revealed that the surface characteristics of biomaterials, such as chemical composition, stiffness, and topography, especially nanotopography, significantly influence cell growth and differentiation. In this study, we examined the effect of surface biomimetic apatite nanostructure of a new hydroxyapatite (HAp) coated genipin-chitosan conjugation scaffold (HGCCS) on cell shape, cytoskeleton organization and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. Cell shape and cytoskeleton organization showed significant differences between cells cultured on genipin-cross-linked chitosan framework (GCF) and those cultured on HGCCS with surface apatite network-like nanostructure after 7 days of incubation in osteogenic media. The result of specific alkaline phosphatase (ALP) activity as an indicator of osteogenic differentiation showed that the ALP activity of rat BMSCs was higher on HGCCS. Based on quantitative real time PCR (RT-PCR), HGCCS induced highest mRNA expression of osteogenic differentiation makers, runt-related transcription factor 2 (Runx2) by 7 days, osteopontin (OPN) by 7 days and osteocalcin (OCN) by 14 days, respectively. The enhanced ability of cells on HGCCS to produce mineralized extracellular matrix and nodules was also assessed on day 14 with Alizarin red staining. The results of this study suggest that the surface biomimetic apatite nanostructure of HGCCS is a critical signal cue to promoting osteogenic differentiation in vitro. These findings open a new research avenue to controlling stem cell lineage commitment and provide a promising scaffold for bone tissue engineering. PMID: 21247339 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Poly(glycerol sebacate)/Gelatin core/shell fibrous structure for regeneration of Myocardial Infarction. Tissue Eng Part A. 2011 Jan 19; Authors: Ravichandran R, Venugopal JR, Subramanian S, Mukherjee S, Ramakrishna S Heart failure remains the leading cause of death in many industrialized nations owing to the inability of the myocardial tissue to regenerate. The main objective of this work was to develop a cardiac patch which is biocompatible and matches the mechanical properties of the heart muscle for myocardial infarction. The present study was to fabricate poly (glycerol sebacate)/gelatin (PGS/gelatin) core/shell fibers and gelatin fibers alone by electrospinning for cardiac tissue engineering. PGS/Gelatin core/shell fibers, PGS used as core polymer to impart the mechanical properties and gelatin as a shell material to achieve favourable cell adhesion and proliferation. These core/shell fibers were characterized by SEM, contact angle, FTIR and tensile testing. The cell-scaffold interactions were analyzed by cell proliferation study, confocal analysis for the expression of cardiac specific marker proteins like Actinin, Troponin-T, Platelet Endothelial Cell Adhesion Molecule (PECAM) and SEM to analyze cell morphology. Dual immunofluorescent staining was performed to further confirm the cardiogenic differentiation of MSCs by employing MSC specific marker protein CD 105 and cardiac specific marker protein Actinin. The results observed that PGS/gelatin core/shell fibers, having good potential biocompatibility and mechanical properties for fabricating nanofibrous cardiac patch and would be a prognosticating device for the restoration of myocardium. Keywords: Cardiac patch, poly(glycerol sebacate), gelatin, core/shell fibers, cardiomyocytes, mesenchymal stem cells. PMID: 21247338 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | High amplitude direct compressive strain enhances mechanical properties of scaffold-free tissue-engineered cartilage. Tissue Eng Part A. 2011 Jan 19; Authors: Hoenig E, Winkler T, Goepfert C, Mielke G, Paetzold H, Schuettler D, Machens HG, Morlock MM, Schilling AF Adult cartilage has a limited healing capacity. Damages resulting from disease or injury increase over time and cause severe pain. One approach to reinstate the cartilage function is tissue-engineering (TE). However, the generation of TE-cartilage is time consuming and expensive and its properties are so far suboptimal. As in vivo cartilage is subject to loading, it is assumed that mechanical stimulation may enhance the quality of TE-cartilage. In this study the short term influence of variable compressive strain amplitudes on mechanical and biochemical properties of scaffold-free TE-cartilage was investigated. Primary porcine chondrocytes were isolated, proliferated, re-differentiated and transferred onto hydroxyapatite carriers, resulting in scaffold-free cartilage-carrier-constructs. These constructs were placed in a custom-made bioreactor. Compression amplitudes of 5%, 10% and 20% were applied. In each experiment four constructs were loaded with dynamic compression (3000 cycles/day, 1Hz) for 14 days and four constructs served as unloaded control. The cartilage was evaluated biochemically, histological and mechanically. No difference in GAG or collagen content between the loaded and the control groups was found. However, a positive correlation between compression amplitude and normalized Young's modulus was detected (R2=0.59, p<0.001). The highest compression amplitude of 20% had the strongest positive effect on the mechanical properties of the TE cartilage (Young's modulus increase of 241±28% compared to unloaded control). The data presented suggest that preconditioning with higher load amplitudes might be an attractive way of generating stiffer tissue and may help accelerating the cultivation of mechanically competent TE-cartilage. PMID: 21247246 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Aligned/Unaligned Conducting Polymer Cryogels with Three-Dimensional Macroporous Architectures from Ice-Segregation-Induced Self-Assembly of PEDOT-PSS. Langmuir. 2011 Jan 19; Authors: Zhang X, Li C, Luo Y Porous conducting polymers are of great interest because of the huge potential to combine high surface areas in the dry state with physical properties relevant to organic electronics. Aligned or unaligned conducting polymer cryogels with 3D macroporous architectures have been prepared using the ice-segregation-induced self-assembly (ISISA) of different poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) freezing precursors as a dispersion or a formed hydrogel. The chemical composition and molecular structure of the resulting conducting polymer cryogels have been investigated by X-ray photoelectron spectroscopy and Raman spectroscopy, respectively. The morphologies of the PEDOT-PSS cryogels, together with their textural structures, have been revealed by scanning electron microscopy, mercury porosimetry, and nitrogen sorption tests. Processing PEDOT-PSS via ISISA endows the conducting polymers with novel properties, as demonstrated by a series of X-ray diffraction, differential scanning calorimetry, and electrical conductivity tests. These conducting polymer cryogels with aligned/unaligned macroporous architectures suggest the potential in the development of electronic components, tissue engineering, and next-generation catalytic and separation supports. PMID: 21247212 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Thermoreversible Hydrogel for In Situ Generation and Release of HepG2 Spheroids. Biomacromolecules. 2011 Jan 19; Authors: Wang D, Cheng D, Guan Y, Zhang Y Organ printing is an alternative to the classic scaffold-based tissue engineering approach in which functional living macrotissues and organ constructs are fabricated by assembly of the building blocks: microtissue spheroids. However, the method for scalable fabrication of cell spheroids does not exist yet. We propose here that it may be a suitable one to generate cell spheroids in thermoreversible hydrogel scaffold, followed by liquefying the scaffold and releasing the generated spheroids. We show that concentrated poly(N-isopropylacrylamide-co-acrylic acid) microgel dispersions solidify upon heating and liquefy upon cooling. A hysteresis in the cooling process was observed and explained by the slow kinetics of the dissolution of the aggregated polymer chains in the cooling process due to additional intra- and interchain interactions. Hep G2 cells are seeded by simple mixing the cells with the microgel dispersions at room temperature. Cell/scaffold constructs form in situ when heated to 37 °C. The cells proliferate and form multicellular spheroids. When brought back to room temperature, the hydrogel scaffolds liquefy, thus, releasing the generated cell spheroids. The released spheroids can attach on the cell culture plate, disassemble, and spread on the substrate, confirming the cell viability. The whole process is carried out under mild conditions and does not involve any toxic additives, which may introduce injury to the cells or DNA. It is scalable and may meet the need for large scale fabrication of cell spheroids for organ printing. PMID: 21247096 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fibrin degradation enhances vascular smooth muscle cell proliferation and matrix deposition in fibrin-based tissue constructs fabricated in vitro. Tissue Eng Part A. 2010 Oct;16(10):3261-70 Authors: Ahmann KA, Weinbaum JS, Johnson SL, Tranquillo RT Completely biological tissue replacements can be fabricated by entrapping cells in a molded fibrin gel. Over time, the fibrin is degraded and replaced with cell-produced extracellular matrix. However, the relationship between fibrin degradation and matrix deposition has not been elucidated. We developed techniques to quantify fibrin degradation products (FDP) and examine plasmin activity in the conditioned medium from fibrin-based constructs. Fibrin-based tissue constructs fabricated with vascular smooth muscle cells (vSMC) were cultured for 5 weeks in the presence of varied concentrations of the fibrinolysis inhibitor -aminocaproic acid and cellularity, and deposited collagen and elastin were measured weekly. These data revealed that increasing concentrations of -aminocaproic acid led to delayed and diminished FDP production, lower vSMC proliferation, and decreased collagen and elastin deposition. FDP were shown to have a direct biological effect on vSMC cultures and vSMC within the fibrin-based constructs. Supplementing construct cultures with 250 or 500μg/mL FDP led to 30% higher collagen deposition than the untreated controls. FDP concentrations as high as 250μg/mL were estimated to exist within the constructs, indicating that FDP generation during remodeling of the fibrin-based constructs exerted direct biological activity. These results help explain many of the positive outcomes reported with fibrin-based tissue constructs in the literature, as well as demonstrate the importance of regulating plasmin activity during their fabrication. PMID: 20536358 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Hemoglobin regulates the metabolic, synthetic, detoxification, and biotransformation functions of hepatoma cells cultured in a hollow fiber bioreactor. Tissue Eng Part A. 2010 Oct;16(10):3231-40 Authors: Chen G, Palmer AF Hepatic hollow fiber (HF) bioreactors constitute one type of extracorporeal bioartificial liver assist device (BLAD). Ideally, cultured hepatocytes in a BLAD should closely mimic the in vivo oxygenation environment of the liver sinusoid to yield a device with optimal performance. However, most BLADs, including hepatic HF bioreactors, suffer from O2 limited transport toward cultured hepatocytes, which reduces their performance. We hypothesize that supplementation of hemoglobin-based O2 carriers into the circulating cell culture medium of hepatic HF bioreactors is a feasible and effective strategy to improve bioreactor oxygenation and performance. We examined the effect of bovine hemoglobin (BvHb) supplementation (15g/L) in the circulating cell culture medium of hepatic HF bioreactors on hepatocyte proliferation, metabolism, and varied liver functions, including biosynthesis, detoxification, and biotransformation. It was observed that BvHb supplementation supported the maintenance of a higher cell mass in the extracapillary space, improved hepatocyte metabolic efficiency (i.e., hepatocytes consumed much less glucose), improved hepatocyte capacity for drug metabolism, and conserved both albumin synthesis and ammonia detoxification functions compared to controls (no BvHb supplementation) under the same experimental conditions. PMID: 20528678 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A preexisting microvascular network benefits in vivo revascularization of a microvascularized tissue-engineered skin substitute. Tissue Eng Part A. 2010 Oct;16(10):3199-206 Authors: Gibot L, Galbraith T, Huot J, Auger FA Delayed or absence of vascularization is one of the major reasons for skin engraftment failure in patients with extensive burns. For such trauma victims, the best alternative to a split-thickness graft would be wound coverage with an autologous in vitro reconstructed skin (RS) combining dermis and epidermis with an appropriate microvascularization. We have developed an endothelialized RS based on our self-assembly approach, which is generated from autologous cultured cells without any exogenous angiogenic growth factor or scaffold. After transplantation in athymic mice, an early inosculation between the graft and host vasculatures occurred within 4 days. We also concurrently detected an active invasion of the dermis by host capillaries sprouting from the wound bed. Thus, the microvascular network constructed in vitro within our three-dimensional skin substitute did not only develop functional anastomoses with the host's blood vessels but also promoted a rapid, complete, and optimal vascularization of the implanted tissues by exerting an angiogenic effect compared with control RS. Our model may bring about interesting possibilities for regenerative medicine by leading to faster vascularization in clinical applications. In addition, the endothelialized RS can be a useful in vitro angiogenesis model. PMID: 20528673 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Colonization and osteogenic differentiation of different stem cell sources on electrospun nanofiber meshes. Tissue Eng Part A. 2010 Oct;16(10):3219-30 Authors: Kolambkar YM, Peister A, Ekaputra AK, Hutmacher DW, Guldberg RE Numerous challenges remain in the successful clinical translation of cell-based therapies for musculoskeletal tissue repair, including the identification of an appropriate cell source and a viable cell delivery system. The aim of this study was to investigate the attachment, colonization, and osteogenic differentiation of two stem cell types, human mesenchymal stem cells (hMSCs) and human amniotic fluid stem (hAFS) cells, on electrospun nanofiber meshes. We demonstrate that nanofiber meshes are able to support these cell functions robustly, with both cell types demonstrating strong osteogenic potential. Differences in the kinetics of osteogenic differentiation were observed between hMSCs and hAFS cells, with the hAFS cells displaying a delayed alkaline phosphatase peak, but elevated mineral deposition, compared to hMSCs. We also compared the cell behavior on nanofiber meshes to that on tissue culture plastic, and observed that there is delayed initial attachment and proliferation on meshes, but enhanced mineralization at a later time point. Finally, cell-seeded nanofiber meshes were found to be effective in colonizing three-dimensional scaffolds in an in vitro system. This study provides support for the use of the nanofiber mesh as a model surface for cell culture in vitro, and a cell delivery vehicle for the repair of bone defects in vivo. PMID: 20504075 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cyclic strain improves strength and function of a collagen-based tissue-engineered vascular media. Tissue Eng Part A. 2010 Oct;16(10):3149-57 Authors: Schutte SC, Chen Z, Brockbank KG, Nerem RM Tissue-engineered blood vessels may provide a solution to the lack of suitable blood vessels for coronary and peripheral vessel bypass grafting. Cyclic strain can be used to provide a more physiological environment that may result in tissue that more closely resembles native artery. In this study, cyclic strain is applied to a collagen-based, tissue-engineered vascular medium. An increased culture time was used to allow the tissue to adhere to the silastic sleeve and to eliminate longitudinal compaction. Cyclic strain improved tissue strength through increased collagen content as well as some radial tissue compaction. Mechanical stimulation promoted a more contractile phenotype and led to a greater contractile response to the vasoconstrictor endothelin-1. PMID: 20504073 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Viable fibroblast matrix patch induces angiogenesis and increases myocardial blood flow in heart failure after myocardial infarction. Tissue Eng Part A. 2010 Oct;16(10):3065-73 Authors: Lancaster J, Juneman E, Hagerty T, Do R, Hicks M, Meltzer K, Standley P, Gaballa M, Kellar R, Goldman S, Thai H This study examines a viable biodegradable three-dimensional fibroblast construct (3DFC) in a model of chronic heart failure. The viable fibroblasts, cultured on a vicryl mesh, secrete growth factors that stimulate angiogenesis. PMID: 20486785 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Moving towards in situ tracheal regeneration: the bionic tissue engineered transplantation approach. J Cell Mol Med. 2010 Jul;14(7):1877-89 Authors: Bader A, Macchiarini P In June 2008, the world's first whole tissue-engineered organ - the windpipe - was successfully transplanted into a 31-year-old lady, and about 18 months following surgery she is leading a near normal life without immunosuppression. This outcome has been achieved by employing three groundbreaking technologies of regenerative medicine: (i) a donor trachea first decellularized using a detergent (without denaturing the collagenous matrix), (ii) the two main autologous tracheal cells, namely mesenchymal stem cell derived cartilage-like cells and epithelial respiratory cells and (iii) a specifically designed bioreactor that reseed, before implantation, the in vitro pre-expanded and pre-differentiated autologous cells on the desired surfaces of the decellularized matrix. Given the long-term safety, efficacy and efforts using such a conventional approach and the potential advantages of regenerative implants to make them available for anyone, we have investigated a novel alternative concept how to fully avoid in vitro cell replication, expansion and differentiation, use the human native site as micro-niche, potentiate the human body's site-specific response by adding boosting, permissive and recruitment impulses in full respect of sociological and regulatory prerequisites. This tissue-engineered approach and ongoing research in airway transplantation is reviewed and presented here. PMID: 20406329 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Simulation of bone tissue formation within a porous scaffold under dynamic compression. Biomech Model Mechanobiol. 2010 Oct;9(5):583-96 Authors: Milan JL, Planell JA, Lacroix D A computational model of mechanoregulation is proposed to predict bone tissue formation stimulated mechanically by overall dynamical compression within a porous polymeric scaffold rendered by micro-CT. Dynamic compressions of 0.5-5% at 0.0025-0.025 s(-1) were simulated. A force-controlled dynamic compression was also performed by imposing a ramp of force from 1 to 70 N. The model predicts homogeneous mature bone tissue formation under strain levels of 0.5-1% at strain rates of 0.0025-0.005 s(-1). Under higher levels of strain and strain rates, the scaffold shows heterogeneous mechanical behaviour which leads to the formation of a heterogeneous tissue with a mixture of mature bone and fibrous tissue. A fibrous tissue layer was also predicted under the force-controlled dynamic compression, although the same force magnitude was found promoting only mature bone during a strain-controlled compression. The model shows that the mechanical stimulation of bone tissue formation within a porous scaffold closely depends on the loading history and on the mechanical behaviour of the scaffold at local and global scales. PMID: 20204446 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Genetically Induced Adult Oligodendrocyte Cell Death Is Associated with Poor Myelin Clearance, Reduced Remyelination, and Axonal Damage. J Neurosci. 2011 Jan 19;31(3):1069-1080 Authors: Pohl HB, Porcheri C, Mueggler T, Bachmann LC, Martino G, Riethmacher D, Franklin RJ, Rudin M, Suter U Loss of oligodendrocytes is a feature of many demyelinating diseases including multiple sclerosis. Here, we have established and characterized a novel model of genetically induced adult oligodendrocyte death. Specific primary loss of adult oligodendrocytes leads to a well defined and highly reproducible course of disease development that can be followed longitudinally by magnetic resonance imaging. Histological and ultrastructural analyses revealed progressive myelin vacuolation, in parallel to disease development that includes motor deficits, tremor, and ataxia. Myelin damage and clearance were associated with induction of oligodendrocyte precursor cell proliferation, albeit with some regional differences. Remyelination was present in the mildly affected corpus callosum. Consequences of acutely induced cell death of adult oligodendrocytes included secondary axonal damage. Microglia were activated in affected areas but without significant influx of B-cells, T-helper cells, or T-cytotoxic cells. Analysis of the model on a RAG-1 (recombination activating gene-1)-deficient background, lacking functional lymphocytes, did not change the observed disease and pathology compared with immune-competent mice. We conclude that this model provides the opportunity to study the consequences of adult oligodendrocyte death in the absence of primary axonal injury and reactive cells of the adaptive immune system. Our results indicate that if the blood-brain barrier is not disrupted, myelin debris is not removed efficiently, remyelination is impaired, and axonal integrity is compromised, likely as the result of myelin detachment. This model will allow the evaluation of strategies aimed at improving remyelination to foster axon protection. PMID: 21248132 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Multipotent adult progenitor cells prevent macrophage-mediated axonal dieback and promote regrowth after spinal cord injury. J Neurosci. 2011 Jan 19;31(3):944-53 Authors: Busch SA, Hamilton JA, Horn KP, Cuascut FX, Cutrone R, Lehman N, Deans RJ, Ting AE, Mays RW, Silver J Macrophage-mediated axonal dieback presents an additional challenge to regenerating axons after spinal cord injury. Adult adherent stem cells are known to have immunomodulatory capabilities, but their potential to ameliorate this detrimental inflammation-related process has not been investigated. Using an in vitro model of axonal dieback as well as an adult rat dorsal column crush model of spinal cord injury, we found that multipotent adult progenitor cells (MAPCs) can affect both macrophages and dystrophic neurons simultaneously. MAPCs significantly decrease MMP-9 (matrix metalloproteinase-9) release from macrophages, effectively preventing induction of axonal dieback. MAPCs also induce a shift in macrophages from an M1, or "classically activated" proinflammatory state, to an M2, or "alternatively activated" antiinflammatory state. In addition to these effects on macrophages, MAPCs promote sensory neurite outgrowth, induce sprouting, and further enable axons to overcome the negative effects of macrophages as well as inhibitory proteoglycans in their environment by increasing their intrinsic growth capacity. Our results demonstrate that MAPCs have therapeutic benefits after spinal cord injury and provide specific evidence that adult stem cells exert positive immunomodulatory and neurotrophic influences. PMID: 21248119 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Species-specific microRNA roles elucidated following astrocyte activation. Nucleic Acids Res. 2011 Jan 18; Authors: Mor E, Cabilly Y, Goldshmit Y, Zalts H, Modai S, Edry L, Elroy-Stein O, Shomron N MicroRNAs (miRNAs) are short non-coding RNAs that play a central role in regulation of gene expression by binding to target genes. Many miRNAs were associated with the function of the central nervous system (CNS) in health and disease. Astrocytes are the CNS most abundant glia cells, providing support by maintaining homeostasis and by regulating neuronal signaling, survival and synaptic plasticity. Astrocytes play a key role in repair of brain insults, as part of local immune reactivity triggered by inflammatory or pathological conditions. Thus, astrocyte activation, or astrogliosis, is an important outcome of the innate immune response, which can be elicited by endotoxins such as lipopolysaccharide (LPS) and cytokines such as interferon-gamma (IFN-γ). The involvement of miRNAs in inflammation and stress led us to hypothesize that astrogliosis is mediated by miRNA function. In this study, we compared the miRNA regulatory layer expressed in primary cultured astrocyte derived from rodents (mice) and primates (marmosets) brains upon exposure to LPS and IFN-γ. We identified subsets of differentially expressed miRNAs some of which are shared with other immunological related systems while others, surprisingly, are mouse and rat specific. Of interest, these specific miRNAs regulate genes involved in the tumor necrosis factor-alpha (TNF-α) signaling pathway, indicating a miRNA-based species-specific regulation. Our data suggests that miRNA function is more significant in the mechanisms governing astrocyte activation in rodents compared to primates. PMID: 21247879 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hydrogel network design using multifunctional macromers to coordinate tissue maturation in ovarian follicle culture. Biomaterials. 2011 Jan 17; Authors: Shikanov A, Smith RM, Xu M, Woodruff TK, Shea LD Synthetic hydrogels with tunable properties are appealing for regenerative medicine. A critical limitation in hydrogel design at low solids concentration is the formation of defects, which increase gelation times and swelling, and reduce elasticity. Here, we report that trifunctional cross-linking peptides applied to 4-arm poly-(ethylene glycol) (PEG) hydrogels decreased swelling and gelation time relative to bi-functional crosslinkers. In contrast to bi-functional peptides, the third cross-linking site on the peptide created a branch point if an intramolecular cross-link formed, which prevented non-functional "dangling-ends" in the hydrogel network and enhanced the number of elastically active cross-links. The improved network formation enabled mouse ovarian follicle encapsulation and maturation in vitro. Hydrogels with bi-functional crosslinkers resulted in cellular dehydration, likely due to osmosis during the prolonged gelation. For trifunctional crosslinkers, the hydrogels supported a 17-fold volumetric expansion of the tissue during culture, with expansion dependent on the ability of the follicle to rearrange its microenvironment, which is controlled through the sensitivity of the cross-linking peptide to the proteolytic activity of plasmin. The improved network design enabled ovarian follicle culture in a completely synthetic system, and can advance fertility preservation technology for women facing premature infertility from anticancer therapies. PMID: 21247629 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hyaluronic acid hydrogels support cord-like structures from endothelial colony-forming cells. Tissue Eng Part A. 2011 Jan 19; Authors: Yee D, Hanjaya-Putra D, Bose V, Luong E, Gerecht S The generation of functional vascular networks has the potential to improve treatment for vascular diseases and to facilitate successful organ transplantation. Endothelial colony-forming cells (ECFCs) have robust proliferative potential and can form vascular networks in vivo. ECFCs are recruited from a bone marrow niche to the site of vascularization, where cues from the extracellular matrix (ECM) instigate vascular morphogenesis. Although this process has been elucidated using natural matrix, little is known about vascular morphogenesis by ECFCs in synthetic matrix, a xeno-free scaffold which can provide a more controllable and clinically relevant alternative for regenerative medicine. We sought to study hyaluronic acid (HA) hydrogels as three-dimensional (3D) scaffolds for capillary-like structure (CLS) formation from ECFCs, and to determine the crucial parameters needed to design such synthetic scaffolds. We found that ECFCs express HA-specific receptors and that vascular endothelial growth factor (VEGF) stimulates hyaluronidase expression in ECFCs. Using a well-defined and controllable 3D HA culture system, we were able to decouple the effect of matrix viscoelasticity from changes in adhesion peptide density. We determined that decreasing matrix viscoelasticity, which corresponds to a loose ultrastructure, significantly increases ECFC vascular tube length and area, and that the effect of local delivery of VEGF within the hydrogel depends on the makeup of the synthetic environment. Collectively, these results set forth initial design criteria that need to be considered in developing vascularized tissue constructs. PMID: 21247340 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Transfusion medicine as a profession: evolution over the past 50 years. Transfusion. 2010 Dec;50(12):2536-41 Authors: Shaz BH, Hillyer CD PMID: 21171234 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Innovation in transfusion medicine and blood banking: documenting the record in 50 years of TRANSFUSION. Transfusion. 2010 Dec;50(12):2542-6 Authors: McCullough J PMID: 20667041 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency next week are expected to approve a plan to compensate some members of its board up to $15,000 a year, but confusion about the pay rate has arisen because of a footnote in the proposal.
The plan would affect six patient advocate members of the 29-member CIRM governing board. The proposal posted on the CIRM web site for the board's Jan. 27 meeting in | | | | | | | | | |  | |  | |  |
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