|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Regenerative nanomedicines: an emerging investment prospective? J R Soc Interface. 2010 Sep 8; Authors: Prescott C Cells respond to their structural surrounding and within nanostructures exhibit unique proliferative and differentiation properties. The application of nanotechnologies to the field of regenerative medicine offers the potential to direct cell fate, target the delivery of cells and reduce immune rejection (via encapsulation), thereby supporting the development of regenerative medicines. The overall objective of any therapy is the delivery of the product not just into the clinic but also to patients on a routine basis. Such a goal typically requires a commercial vehicle and substantial levels of investment in scientific, clinical, regulatory and business expertise, resources, time and funding. Therefore, this paper focuses on some of the challenges facing this emerging industry, including investment by the venture capital community. PMID: 20826478 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine. Opportunities and challenges: a brief overview. J R Soc Interface. 2010 Sep 8; Authors: Polak DJ Regenerative medicine is a new multi-disciplinary field aiming at the repair or replacement of disease body parts. The field is progressing at an unprecedented pace and although the opportunities are immense, many hurdles lie ahead. This brief review analyses the opportunities and challenges faced by regenerative medicine. PMID: 20826477 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Preparation and characterization of NaOH treated micro-fibrous polyethylene terephthalate nonwovens for biomedical application. J Mech Behav Biomed Mater. 2010 Nov;3(8):574-83 Authors: Hadjizadeh A, Ajji A, Bureau MN Recently, micro-fibrous polyethylene terephthalate nonwovens have been investigated and applied in many biotechnological and biomedical applications. NaOH treatment has been used as a simple and cost effective method to alter surface properties, in order to overcome their surface inertness. However, the effects of this treatment on the matrices mechanical and physical properties; particularly, those composed of fibers with small diameter (<20 μm); have been poorly investigated. This study investigates the variations, imposed by the NaOH treatment, in the physical and tensile properties of micro-fibrous polyethylene terephthalate mats. Polyethylene terephthalate webs with two different average fiber diameters of 6±2.5 and 10±4 μm were produced by melt blowing process. A number of these webs were consolidated to prepare fibrous matrices using a thermal treatment. The matrices were treated using NaOH 1 N at 65 °C for various durations (ranging from 20 min to 24 h). In addition to their physical properties such as weight loss, thickness, porosity, shrinkage and surface density; their morphology and tensile properties were also evaluated using scanning electron microscopy and micromechanical tester, respectively. In general, by increasing treatment duration, weight loss, porosity, and shrinkage increased, while thickness and density decreased. As a result of treatment duration, pores appeared on the surface of individual fibers, and tensile stress and Young's modulus decreased while tensile strain increased. Mats with different fiber diameters showed different physical and mechanical properties. These findings suggested that the structure of the matrices and the properties required for its end use, for biomedical applications including scaffolding materials for tissue engineering, should be considered in selecting NaOH treatment condition. PMID: 20826363 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Derivation, characterization, and gene expression profile of two new human ES cell lines from India. Stem Cell Res. 2010 Aug 1; Authors: Mandal A, Bhowmik S, Patki A, Viswanathan C, Majumdar AS Human embryonic stem cells (hESCs) offer new avenues for studying human development and disease progression in addition to their tremendous potential toward development of cell-replacement therapies for various cellular disorders. We have earlier reported the derivation and characterization of Relicell(®) hES1, the first fully characterized hESC line generated from the Indian subcontinent. Recent studies have demonstrated discrete differences among hESC lines, in terms of both their growth properties and their differentiation propensity. To address some of these issues in the context of hESC research in India, we have recently generated two new hESC lines: Relicell(®) hES2 and Relicell(®)hES3. Both these cell lines were derived using a combinatorial approach of immunosurgery followed by mechanical surgery for inner cell mass isolation. The cell lines exhibit the usual hESC characteristics including their ability to differentiate both in vitro and in vivo to yield the three germinal layers. Whole genome microarray analysis of these cell lines was compared with Relicell(®)hES1 and it showed that approximately 9000 genes were expressed by these lines. As expected the expression pattern of these new cell lines bore close resemblance to that of Relicell(®)hES1. A majority of the pluripotency genes and the genes known to inhibit various differentiation pathways were also expressed by these cell lines. We also observed that each of these cell lines expressed a unique set of genes that are mutually exclusive from each other. These results represent the first detailed characterization of a set of hESC lines originating from India. PMID: 20826120 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine: Then and now - an update of recent history into future possibilities. J Cell Mol Med. 2010 Sep 1; Authors: Polykandriotis E, Popescu LM, Horch RE Abstract The fields of tissue engineering and regenerative medicine are yet to bring about the anticipated therapeutic revolution. After two decades of extremely high expectations and often disappointing returns both in the medical as well as in the financial arena, this scientific field reflects the sense of a new era and suggests the feeling of making a fresh start while many scientists are probably seeking reorientation. Much of research was industry driven, so that especially in the aftermath of the recent financial meltdown in the last 2 years we have witnessed a biotech asset yard sale. In spite of any monetary shortcomings, from a technological point of view there have been great leaps that are yet to find their way to the patient. Regenerative medicine is definitely bound to play a major role in our life because it embodies one of the primordial dreams of mankind, such as: ever lasting youth, flying, remote communication and setting foot on the moon. The Journal of Cellular and Molecular Medicine has been at the frontier of these developments in Tissue Engineering and Regenerative Medicine from its beginning and reflects recent scientific advances in both fields. Therefore this review tries to look at regenerative medicine through the keyhole of history which might just be like looking "back to the future". PMID: 20825521 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Design of Nano- and Micro-fiber Combined Scaffolds by Electrospinning of Collagen onto Starch-based Fiber Meshes: A Man-made Equivalent of Natural Extracellular Matrix. Tissue Eng Part A. 2010 Sep 9; Authors: Tuzlakoglu K, Santos MI, Neves NM, Reis RL Mimicking the structural organization and biologic function of natural extracellular matrix (ECM) has been one of the main goals of tissue engineering. Nevertheless, the majority of scaffolding materials for bone regeneration highlights biochemical functionality in detriment of mechanical properties. In this work we present a rather innovative construct that combines in the same structure electrospun type I collagen nano-fibers with starch-based micro-fibers. These combined structures were obtained by a two step methodology and structurally consist in a type I collagen nano-network incorporated on a macro starch-based support. The morphology of the developed structures was assessed by several microscopy techniques and the collagenous nature of the nano-network was confirmed by immunohistochemistry. In addition, and especially regarding the requirements of large bone defects, we also successfully introduced the concept of layer-by-layer, as a way to produce thicker structures. In an attempt to recreate bone microenvironment the design and biochemical composition of the combined structures also envisioned bone forming cells and endothelial cells (ECs). The inclusion of a type I collagen nano-network induced a stretched morphology and improved the metabolic activity of osteoblasts. Regarding ECs, the presence of type I collagen on the combined structures provided adhesive support and obviated the need of pre-coating with fibronectin. It was also importantly observed that ECs on the nano-network organized into circular structures, a 3D arrangement distinct from that observed for osteoblasts and resembling the microcappillary-like organizations formed during angiogenesis. By providing simultaneously physical and chemical cues for cells, the herein proposed combined structures hold a great potential in bone regeneration as a man-made equivalent of ECM. PMID: 20825361 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Heterotopic autologous chondrocyte transplantation - a realistic approach to support articular cartilage repair? Tissue Eng Part B Rev. 2010 Sep 9; Authors: El Sayed K, Haisch A, John T, Marzahn U, Lohan A, Mueller RD, Kohl B, Ertel W, Stoelzel K, Schulze-Tanzil G Injured articular cartilage is limited in it's capacity to heal. Autologous chondrocyte transplantation (ACT) is a suitable technique for cartilage repair, but it requires articular cartilage biopsies for sufficient autologous chondrocyte expansion in vitro. Hence ACT is restricted by donor site morbidity and autologous articular chondrocytes availability. The use of non-articular heterotopic (h) chondrocytes such as auricular, nasoseptal or costal chondrocytes for ACT might overcome these limitations: heterotopic sources show lesser donor site morbidity and a comparable extracellular cartilage matrix (ECM) synthesis profile to articular cartilage. However heterotopic (h)ACT poses a challenge. Particular tissue characteristics of heterotopic cartilage, divergent culturing peculiarities of heterotopic chondrocytes and the advantages and drawbacks related to these diverse cartilage sources were critically discussed. Finally, available in vitro and in vivo experimental heterotopic (h)ACT approaches were summarized. The quality of the cartilage engineered using heterotopic chondrocytes remains partly controversy due to the divergent methodologies and culture conditions used. While some encouraging in vivo results using (h)ACT have been demonstrated, standardized culturing protocols are strongly required. However, whether heterotopic chondrocytes implanted into joint cartilage defects maintain their particular tissue properties or can be adapted via tissue engineering strategies to fulfil regular articular cartilage functions requires further studies. PMID: 20825360 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | HIV-1-derived lentiviral vectors directly activate plasmacytoid dendritic cells, which in turn induce the maturation of myeloid dendritic cells. Hum Gene Ther. 2010 Sep 8; Authors: Rossetti M, Gregori S, Hauben E, Sergi Sergi L, Brown BD, Naldini L, Roncarolo MG Lentiviral vectors (LV) can induce type I interferon (IFN I) production from murine plasmacytoid dendritic cells (pDC), but not myeloid (my)DC. Here, we investigated whether this mechanism is conserved in human DC. MyDC and pDC were isolated from peripheral blood, and transduced with increasing vector concentrations. Compared to in vitro differentiated monocyte-derived DC, the transduction efficiency of peripheral blood DC was low (ranging from <1 to 45%), with pDC showing the lowest susceptibility to LV transduction. Phenotype and function of myDC were not directly modified by LV transduction; by contrast, pDC produced significant levels of IFN-α and TNF-α. pDC activation was dependent on functional vector particles and was mediated by TLR7/9 triggering. Co-culture of myDC with pDC in the presence of LV resulted in myDC activation, with CD86 up-regulation and IL-6 secretion. These findings demonstrate that the induction of transgene-specific immunity is triggered by an innate immune response with pDC activation and consequent myDC maturation, a response that closely resembles the one induced by functional viruses. This information is important to design strategies aimed at using LV in humans for gene therapy, where adverse immune responses must be avoided, or for cancer immunotherapy, where inducing immunity is the goal. PMID: 20825284 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Characterization of micropatterned nanofibrous scaffolds for neural network activity readout for high-throughput screening. J Biomed Mater Res B Appl Biomater. 2010 Jul;94(1):238-49 Authors: Wang L, Kisaalita WS Micropatterns were fabricated in nanofibrous poly-L-lactic acid (PLLA) films by laser micromachining and the resulting scaffolds were characterized with respect to architecture, thermal, mechanical, and mass transport properties. Also, human neural stem cells were successfully cultured in these micropatterned nanofibrous scaffolds (MNFSs). The scaffolds were incorporated in high-density well plates (e.g., 96-well plates), creating a platform for high-throughput screening of drugs with physiologically more relevant networked neural cultures. Through mathematical modeling of the transport of model stimulants, the feasibility of stimulating neural networks cultured in MNFSs was demonstrated. More work is needed to establish biological network activity-MNFS architecture relationships. PMID: 20524200 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cryopreserved lip mucosa tissue derived keratinocytes can fabricate tissue engineered palatal mucosa equivalent. J Biomed Mater Res B Appl Biomater. 2010 Jul;94(1):165-70 Authors: Xiong X, Jia J, He S, Zhao Y Clinical application of tissue engineered palatal mucosa is hampered by unavailability of suitable oral keratinocytes as seeding cells. The aim of this study is to fabricate a tissue engineered palatal mucosa equivalent from the oral keratinocytes which cultured from cryopreserved lip mucosa tissues. Abundant lip mucosa tissues during cheilorrhaphy were firstly cryopreserved in liquid nitrogen for four to six months, and then recovered to culture oral keratinocytes for the fabrication of oral mucosa equivalent. In the control groups, oral keratinocytes cultured from fresh lip mucosa, fresh palate mucosa, and cryopreserved palate mucosa were used to fabricate oral mucosa equivalents. Attachment rate of the oral keratinocytes derived from cryopreserved lip mucosa was lower than that of the keratinocytes from fresh lip mucosa samples, however, the cell cycle distribution of oral keratinocytes cultured from all four groups of mucosa samples were similar. Histologically, the fabricated mucosa equivalents from these four groups had four- to six epithelial layers, the basal cells were cubic and the outmost cells were flatten with narrow nuclei which paralleled to the surface of the dermal matrix. Additionally, Ki-67 positive stained cells were mainly located in the basal layer of the epithelium of these equivalents. These characteristics disclosed that the oral mucosa equivalent cultured from the cryopreserved lip mucosa tissue was not different with the equivalents from other groups and similar to the native palate mucosa tissue. It suggested that the cryopreserved lip mucosa tissues could be used for the construction of palatal mucosal equivalent for clinical application. PMID: 20524191 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Designing poly[(R)-3-hydroxybutyrate]-based polyurethane block copolymers for electrospun nanofiber scaffolds with improved mechanical properties and enhanced mineralization capability. J Phys Chem B. 2010 Jun 10;114(22):7489-98 Authors: Liu KL, Choo ES, Wong SY, Li X, He CB, Wang J, Li J Efforts to mineralize electrospun hydrophobic polyester scaffold often require prior surface modification such as plasma or alkaline treatment, which may affect the mechanical integrity of the resultant scaffold. Here through rational design we developed a series of polyurethane block copolymers containing poly[(R)-3-hydroxybutyrate] (PHB) as hard segment and poly(ethylene glycol) (PEG) as soft segment that could be easily fabricated into mineralizable electrospun scaffold without the need of additional surface treatment. To ensure that the block copolymers do not swell excessively in water, PEG content in the polymers was kept below 50 wt %. To obtain good dry and hydrated state mechanical properties with limited PEG, low-molecular-weight PHB-diol with M(n) 1230 and 1790 were used in various molar feed ratios. The macromolecular characteristics of the block copolymers were confirmed by (1)H NMR spectroscopy, gel permeation chromatography (GPC), and thermal gravimetric analyses (TGA). With the incorporation of the hydrophilic PEG segments, the surface and bulk hydrophilicity of the block copolymers were significantly improved. Differential scanning calorimetry (DSC) revealed that the block copolymers had low PHB crystallinity and no PEG crystallinity. This was further confirmed by X-ray diffraction analyses (XRD) in both dry and hydrated states. With short PHB segments and soft PEG coupled together, the block copolymers were no longer brittle. Tensile measurements showed that the block copolymers with higher PEG content or shorter PHB segments were more ductile. Furthermore, their ductility was enhanced in hydrated states with one particular example showing increment in strain at break from 1090 to 1962%. The block copolymers were fabricated into an electrospun fibrous scaffold that was easily mineralized by simple incubation in simulated body fluid. The materials have good potential for bone regeneration application and may be extended to other applications by simply coating them with other biologically active substances. PMID: 20469884 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Use of synovium-derived stromal cells and chitosan/collagen type I scaffolds for cartilage tissue engineering. Biomed Mater. 2010 Sep 9;5(5):055005 Authors: Gong Z, Xiong H, Long X, Wei L, Li J, Wu Y, Lin Z The objective was to investigate synovium-derived stromal cells (SDSCs) coupled with chitosan/collagen type I (CS/COL-I) scaffolds for cartilage engineering. CS/COL-I scaffolds were fabricated through freeze-drying and cross-linked by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. SDSCs were isolated from synovium and cultured onto CS/COL-I scaffolds, constructs of which were incubated in serum-free chondrogenic medium with sequential application of TGF-β1 and bFGF for up to 21 days and then implanted into nude mice. The physical characteristics of the scaffolds were examined. The quality of the in vitro constructs was assessed in terms of DNA content by PicoGreen assay and cartilaginous matrix by histological examination. The implants of the constructs were evaluated by histological and immunohistochemical examinations and reverse transcription PCR. Results indicated that the CS/COL-I scaffold showed porous structures, and the DNA content of SDSCs in CS/COL-I scaffolds increased at 1 week culture time. Both of the constructs in vitro and the implants were examined with positive stained GAGs histologically and the implants with positive collagen type II immunohistochemically. RT-PCR of the implants indicated that aggrecan and collagen type II expressed. It suggested that SDSCs coupled with CS/COL-I scaffolds treated sequentially with TGF-β1 and bFGF in vitro were highly competent for engineered cartilage formation in vitro and in vivo. PMID: 20826911 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Preparation and characterization of chitosan-heparin composite matrices for blood contacting tissue engineering. Biomed Mater. 2010 Sep 9;5(5):055001 Authors: He Q, Ao Q, Gong K, Zhang L, Hu M, Gong Y, Zhang X Chitosan has been widely used for biomaterial scaffolds in tissue engineering because of its good mechanical properties and cytocompatibility. However, the poor blood compatibility of chitosan has greatly limited its biomedical utilization, especially for blood contacting tissue engineering. In this study, we exploited a polymer blending procedure to heparinize the chitosan material under simple and mild conditions to improve its antithrombogenic property. By an optimized procedure, a macroscopically homogeneous chitosan-heparin (Chi-Hep) blended suspension was obtained, with which Chi-Hep composite films and porous scaffolds were fabricated. X-ray photoelectron spectroscopy and sulfur elemental analysis confirmed the successful immobilization of heparin in the composite matrices (i.e. films and porous scaffolds). Toluidine blue staining indicated that heparin was distributed homogeneously in the composite matrices. Only a small amount of heparin was released from the matrices during incubation in normal saline for 10 days. The composite matrices showed improved blood compatibility, as well as good mechanical properties and endothelial cell compatibility. These results suggest that the Chi-Hep composite matrices are promising candidates for blood contacting tissue engineering. PMID: 20826908 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Pyramidal neurons are generated from oligodendroglial progenitor cells in adult piriform cortex. J Neurosci. 2010 Sep 8;30(36):12036-49 Authors: Guo F, Maeda Y, Ma J, Xu J, Horiuchi M, Miers L, Vaccarino F, Pleasure D Previous studies have shown that oligodendroglial progenitor cells (OPCs) can give rise to neurons in vitro and in perinatal cerebral cortex in vivo. We now report that OPCs in adult murine piriform cortex express low levels of doublecortin, a marker for migratory and immature neurons. Additionally, these OPCs express Sox2, a neural stem cell marker, and Pax6, a transcription factor characteristic of progenitors for cortical glutamatergic neurons. Genetic fate-mapping by means of an inducible Cre-LoxP recombination system proved that these OPCs differentiate into pyramidal glutamatergic neurons in piriform cortex. Several lines of evidence indicated that these newly formed neurons became functionally integrated into the cortical neuronal network. Our data suggest that NG2(+)/PDGFRα(+) proteolipid protein promoter-expressing progenitors generate pyramidal glutamatergic neurons within normal adult piriform cortex. PMID: 20826667 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells. J R Soc Interface. 2010 Sep 8; Authors: Stephenson E, Ogilvie CM, Patel H, Cornwell G, Jacquet L, Kadeva N, Braude P, Ilic D The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scaling-up cell expansion for that purpose. We have to be certain that the genome of the starting material is stable and normal, but the limited resolution of conventional karyotyping is unable to give us such assurance. Advanced molecular cytogenetic technologies such as array comparative genomic hybridization for identifying chromosomal imbalances, and single nucleotide polymorphism analysis for identifying ethnic background and loss of heterozygosity should be introduced as obligatory diagnostic tests for each newly derived hESC line before it is deposited in national stem cell banks. If this new quality standard becomes a requirement, as we are proposing here, it would facilitate and accelerate the banking process, since end-users would be able to select the most appropriate line for their particular application, thus improving efficiency and streamlining the route to manufacturing therapeutics. The pharmaceutical industry, which may use hESC-derived cells for drug screening, should not ignore their genomic profile as this may risk misinterpretation of results and significant waste of resources. PMID: 20826474 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy. Hum Gene Ther. 2010 Sep 8; Authors: Hodgkinson CP, Gomez JA, Mirotsou M, Dzau V The use of stem cells for tissue regeneration and repair is advancing both in the bench and in the bedside. Stem cells isolated from bone marrow are currently tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, neurological, kidney failure, cancer, and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis in genetic modifications aimed to improve survival, homing, angiogenesis and improving heart function after myocardial infarction. The advancements in other disease areas are also summarized. PMID: 20825283 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Wound care: the role of advanced wound healing technologies. J Vasc Surg. 2010 Sep;52(3 Suppl):59S-66S Authors: Wu SC, Marston W, Armstrong DG Wound repair and regeneration is a highly complex combination of matrix destruction and reorganization. While major hurdles remain, advances over the past generation have improved the clinician's armamentarium in the medical and surgical management of this problem. The purpose of this manuscript is to review the current literature regarding the pragmatic use of three of the most commonly employed advanced therapies; namely, bioengineered tissue, negative pressure wound therapy, and hyperbaric oxygen therapy with a focus on the near-term future of wound healing, including stem cell therapy. PMID: 20804934 [PubMed - in process] | | | | | | | | | |  | |  | |  |
No comments:
Post a Comment