|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | The Matrix-Binding Domain of Microfibril-Associated Glycoprotein-1 Targets Active Connective Tissue Growth Factor to a Fibroblast-Produced Extracellular Matrix. Macromol Biosci. 2010 Aug 26; Authors: Weinbaum JS, Tranquillo RT, Mecham RP It is advantageous to use biomaterials in tissue engineering that stimulate extracellular matrix (ECM) production by the cellular component. Connective tissue growth factor (CTGF) stimulates type I collagen (COL1A1) transcription, but is functionally limited as a free molecule. Using a matrix-binding domain (MBD) from microfibril-associated glycoprotein-1, the fusion protein MBD-CTGF was targeted to the ECM and tested for COL1A1 transcriptional activation. MBD-CTGF produced by the ECM-synthesizing fibroblasts, or provided exogenously, localized to the elastic fiber ECM. MBD-CTGF, but not CTGF alone, led to a two-fold enhancement of COL1A1 expression. This study introduces a targeting technology that can be used to elevate collagen transcription in engineered tissues and thereby improve tissue mechanics. PMID: 20799254 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Melt Processing of Chitosan-Based Fibers and Fiber-Mesh Scaffolds for the Engineering of Connective Tissues. Macromol Biosci. 2010 Aug 26; Authors: Correlo VM, Costa-Pinto AR, Sol P, Covas JA, Bhattacharya M, Neves NM, Reis RL We report the production of chitosan-based fibers and chitosan fiber-mesh structures by melt processing (solvent-free) to be used as tissue-engineering scaffolds. The melt-based approach used to produce the scaffolds does not change their main characteristics, including the surface roughness and microporosity. The porosity, pore size, interconnectivity and mechanical performance of the scaffolds are all within the range required for various tissue-engineering applications. Biological assessments are performed in direct-contact assays. Cells are able to colonize the scaffold, including the inner porous structure. The cells show high indices of viability in all of the scaffold types. PMID: 20799253 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A Study on Repair of Porcine Articular Cartilage Defects With Tissue-Engineered Cartilage Constructed In Vivo By Composite Scaffold Materials. Ann Plast Surg. 2010 Aug 25; Authors: Lin PB, Ning LJ, Lian QZ, Xia Z, Xin Y, Sen BH, Fei NF The study was performed to find out a promising injectable composite scaffold for cartilage tissue engineering. By using a composite of allogenous cartilage microparticle acellular tissue matrix (CMACTM) and fibrin glue (Fg) as injectable scaffold materials, tissue-engineered cartilage was constructed in vivo, and the effects of which on the repair of porcine articular cartilage defects were observed.CMACTM was obtained from domestic pigs. The chondrocytes were prepared from experimental mini-type pigs and expanded in vitro. Fg was used as a scaffold material. The composite of CMACTM, second-passage chondrocytes, and Fg was replanted to the articular cartilage defective regions in autologous mini-type pig by injection. At 12 weeks after replantation, samples were collected and analyzed by general observation and histologic staining.The constructed tissue-engineered cartilage exhibited a good efficiency in the repair of articular cartilage defects. Cells in the constructed tissue-engineered cartilage grew well and were able to secrete cartilaginous matrix. The tissue-engineered cartilage showed a better biologic performance than the control.A composite of allogenous CMACTM and Fg was a promising injectable scaffold for cartilage tissue engineering, which could be used to repair articular cartilage defects by a minimally invasive procedure. PMID: 20798625 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioactive polymer/extracellular matrix scaffolds fabricated with a flow perfusion bioreactor for cartilage tissue engineering. Biomaterials. 2010 Aug 24; Authors: Liao J, Guo X, Grande-Allen KJ, Kasper FK, Mikos AG In this study, electrospun poly(varepsilon-caprolactone) (PCL) microfiber scaffolds, coated with cartilaginous extracellular matrix (ECM), were fabricated by first culturing chondrocytes under dynamic conditions in a flow perfusion bioreactor and then decellularizing the cellular constructs. The decellularization procedure yielded acellular PCL/ECM composite scaffolds containing glycosaminoglycan and collagen. PCL/ECM composite scaffolds were evaluated for their ability to support the chondrogenic differentiation of mesenchymal stem cells (MSCs) in vitro using serum-free medium with or without the addition of transforming growth factor-beta1 (TGF-beta1). PCL/ECM composite scaffolds supported chondrogenic differentiation induced by TGF-beta1 exposure, as evidenced in the up-regulation of aggrecan (11.6 +/- 3.8 fold) and collagen type II (668.4 +/- 317.7 fold) gene expression. The presence of cartilaginous matrix alone reduced collagen type I gene expression to levels observed with TGF-beta1 treatment. Cartilaginous matrix further enhanced the effects of growth factor treatment on MSC chondrogenesis as evidenced in the higher glycosaminoglycan synthetic activity for cells cultured on PCL/ECM composite scaffolds. Therefore, flow perfusion culture of chondrocytes on electrospun microfiber scaffolds is a promising method to fabricate polymer/extracellular matrix composite scaffolds that incorporate both natural and synthetic components to provide biological signals for cartilage tissue engineering applications. PMID: 20797784 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Penile Enhancement Using Autologous Tissue Engineering with Biodegradable Scaffold: A Clinical and Histomorphometric Study. J Sex Med. 2009 Oct 19; Authors: Perovic SV, Sansalone S, Djinovic R, Ferlosio A, Vespasiani G, Orlandi A Introduction. Autologous tissue engineering with biodegradable scaffolds is a new treatment option for real penile girth enhancement. Aim. The aim of this article is to evaluate tissue remodeling after penile girth enhancement using this technique. Methods. Between June 2005 and May 2007, a group of 12 patients underwent repeated penile widening using biodegradable scaffolds enriched with expanded autologous scrotal dartos cells. Clinical monitoring was parallel to histological investigation of tissue remodeling. During second surgical procedure, biopsies were obtained 10-14 months after first surgery (mean 12 months, N = 6) and compared with those obtained after 22-24 months (mean 23 months, N = 6), and control biopsies from patients who underwent circumcision (N = 5). Blind evaluation of histomorphometrical and immunohistochemical finding was performed in paraffin sections. Main Outcome Measurements. Penile girth gain in a flaccid state ranged between 1.5 and 3.8 cm (mean 2.1 +/- 0.28 cm) and in full erection between 1.2 and 4 cm (mean 1.9 +/- 0.28 cm). Patients' satisfaction, defined by a questionnaire, was good (25%) and very good (75%). Results. In biopsies obtained 10-14 months after first surgery, highly vascularized loose tissue with collagen deposition associated with small foci of mild chronic and granulomatous inflammation surrounding residual amorphous material was observed. Fibroblast-like hyperplasia and small vessel neoangiogenesis occurred intimately associated with the progressive growth of vascular-like structures from accumulation of CD34 and alpha-smooth muscle actin-positive cells surrounding residual scaffold-like amorphous material. Capillary neoangiogenesis occurred inside residual amorphous material. In biopsies obtained after 22-24 months, inflammation almost disappeared and tissue closely resembled that of the dartos fascia of control group. Conclusions. Autologous tissue engineering using expanded scrotal dartos cells with biodegradable scaffolds is a new and promising method for penile widening that generates progressive accumulation of stable collagen-rich, highly vascularized tissue matrix that closely resemble deep dartos fascia. Perovic SV, Sansalone S, Djinovic R, Ferlosio A, Vespasiani G, and Orlandi A. Penile enhancement using autologous tissue engineering with biodegradable scaffold: A clinical and histomorphometric study. J Sex Med **;**:**-**. PMID: 20796201 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Melt Processing of Chitosan-Based Fibers and Fiber-Mesh Scaffolds for the Engineering of Connective Tissues. Macromol Biosci. 2010 Aug 26; Authors: Correlo VM, Costa-Pinto AR, Sol P, Covas JA, Bhattacharya M, Neves NM, Reis RL We report the production of chitosan-based fibers and chitosan fiber-mesh structures by melt processing (solvent-free) to be used as tissue-engineering scaffolds. The melt-based approach used to produce the scaffolds does not change their main characteristics, including the surface roughness and microporosity. The porosity, pore size, interconnectivity and mechanical performance of the scaffolds are all within the range required for various tissue-engineering applications. Biological assessments are performed in direct-contact assays. Cells are able to colonize the scaffold, including the inner porous structure. The cells show high indices of viability in all of the scaffold types. PMID: 20799253 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Translation of science to surgery: LINKING EMERGING CONCEPTS IN BIOLOGICAL CARTILAGE REPAIR TO SURGICAL INTERVENTION. J Bone Joint Surg Br. 2010 Sep;92(9):1195-202 Authors: Moran CJ, Shannon FJ, Barry FP, O'Byrne JM, O'Brien T, Curtin W Orthopaedic surgery is in an exciting transitional period as modern surgical interventions, implants and scientific developments are providing new therapeutic options. As advances in basic science and technology improve our understanding of the pathology and repair of musculoskeletal tissue, traditional operations may be replaced by newer, less invasive procedures which are more appropriately targeted at the underlying pathophysiology. However, evidence-based practice will remain a basic requirement of care. Orthopaedic surgeons can and should remain at the forefront of the development of novel therapeutic interventions and their application. Progression of the potential of bench research into an improved array of orthopaedic treatments in an effective yet safe manner will require the development of a subgroup of specialists with extended training in research to play an important role in bridging the gap between laboratory science and clinical practice. International regulations regarding the introduction of new biological treatments will place an additional burden on the mechanisms of this translational process, and orthopaedic surgeons who are trained in science, surgery and the regulatory environment will be essential. Training and supporting individuals with these skills requires special consideration and discussion by the orthopaedic community. In this paper we review some traditional approaches to the integration of orthopaedic science and surgery, the therapeutic potential of current regenerative biomedical science for cartilage repair and ways in which we may develop surgeons with the skills required to translate scientific discovery into effective and properly assessed orthopaedic treatments. PMID: 20798434 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Early mammalian erythropoiesis requires the Dot1L methyltransferase. Blood. 2010 Aug 26; Authors: Feng Y, Yang Y, Ortega MM, Copeland JN, Zhang M, Jacob JB, Fields TA, Vivian JL, Fields PE Histone methylation is an important regulator of gene expression, and its coordinated activity is critical in complex developmental processes such as hematopoiesis. Disruptor of Telomere Silencing 1-Like (DOT1L) is a unique histone methyltransferase that specifically methylates histone H3 at lysine 79. We analyzed Dot1L mutant mice to determine the influence of this enzyme on embryonic hematopoiesis. The mutant mice developed more slowly than wildtype embryos and died between E10.5 and E13.5, displaying a striking anemia, especially apparent in the small vessels of the yolk sac. Further, a severe, selective defect in erythroid, but not myeloid differentiation was observed. The erythroid progenitors failed to develop normally, demonstrating retarded progression through the cell cycle, accumulation during the G(0)/G(1) stage, and a marked increase in apoptosis in response to erythroid growth factors. GATA2, a factor essential for early erythropoiesis, was significantly reduced in Dot1L-deficient cells, while expression of PU.1, a transcription factor that inhibits erythropoiesis and promotes myelopoiesis, was increased. These data suggest a model whereby DOT1L-dependent H3K79 methylation serves as a critical regulator of a differentiation switch during early hematopoiesis, regulating steady-state levels of GATA2 and PU.1 transcription and thus controlling the numbers of circulating erythroid and myeloid cells. PMID: 20798234 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human Artificial Chromosome with a Conditional Centromere for Gene Delivery and Gene Expression. DNA Res. 2010 Aug 26; Authors: Iida Y, Kim JH, Kazuki Y, Hoshiya H, Takiguchi M, Hayashi M, Erliandri I, Lee HS, Samoshkin A, Masumoto H, Earnshaw WC, Kouprina N, Larionov V, Oshimura M Human artificial chromosomes (HACs), which carry a fully functional centromere and are maintained as a single-copy episome, are not associated with random mutagenesis and offer greater control over expression of ectopic genes on the HAC. Recently, we generated a HAC with a conditional centromere, which includes the tetracycline operator (tet-O) sequence embedded in the alphoid DNA array. This conditional centromere can be inactivated, loss of the alphoid(tet)(-)(O) (tet-O HAC) by expression of tet-repressor fusion proteins. In this report, we describe adaptation of the tet-O HAC vector for gene delivery and gene expression in human cells. A loxP cassette was inserted into the tet-O HAC by homologous recombination in chicken DT40 cells following a microcell-mediated chromosome transfer (MMCT). The tet-O HAC with the loxP cassette was then transferred into Chinese hamster ovary cells, and EGFP transgene was efficiently and accurately incorporated into the tet-O HAC vector. The EGFP transgene was stably expressed in human cells after transfer via MMCT. Because the transgenes inserted on the tet-O HAC can be eliminated from cells by HAC loss due to centromere inactivation, this HAC vector system provides important novel features and has potential applications for gene expression studies and gene therapy. PMID: 20798231 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Ultrasonography in Regenerative Injection (Prolotherapy) Using Dextrose, Platelet-rich Plasma, and Other Injectants. Phys Med Rehabil Clin N Am. 2010 Aug;21(3):585-605 Authors: Fullerton BD, Reeves KD Recent advances in ultrasound technology are leading physiatrists to new understandings of pain sources, new treatment options, and the ability to guide soft tissue interventions. This article examines the role of imaging ultrasound in diagnosing soft tissue injury and disease that may respond to regenerative medicine techniques (known as prolotherapy) using injectants such as dextrose, morrhuate sodium, or platelet-rich plasma. The current state of ultrasound evidence for these interventions is reviewed. Case examples assist in understanding clinical applications that currently outpace the evidence base. Development of quantitative ultrasound measures to objectively evaluate soft tissue organization is discussed. PMID: 20797551 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells. Cytotherapy. 2010 Aug 26; Authors: Rasmussen JG, Frøbert O, Pilgaard L, Kastrup J, Simonsen U, Zachar V, Fink T Abstract Background aims. Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media. Methods. The effects of prolonged hypoxic culture on growth and pro-angiogenic properties were investigated using human ASC cultured at 1%, 5% and 21% oxygen. The effect of trypsinization on the expression of pro-angiogenic genes was also determined. Results. Trypsinization induced up-regulation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) genes independent of oxygen concentration. The expression of VEGF and IGF-1 was up-regulated in ASC cultured at 1% oxygen for 13 days compared with 4 days. The VEGF concentration in ASC-conditioned media was higher after prolonged hypoxic culture compared with short-term culture, while the IGF-1 and chemokine (CXC motif) ligand 12 (CXCL12) concentrations were unchanged. The VEGF receptor blocker SU5416 abolished angiogenesis in a cultured rat aortic ring model. Media from cells exposed to hypoxia increased angiogenesis, an effect that was dependent on factors other than just the VEGF concentration in the added media. Conclusions. Optimization of the angiogenic potential of stem cell-based therapy in the treatment of vascular disease is important. We have demonstrated that prolonged hypoxic culture and trypsinization augment the therapeutic angiogenic potential of ASC. PMID: 20795759 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose tissue-derived stem cells show both immunogenic and immunosuppressive properties after chondrogenic differentiation. Cytotherapy. 2010 Aug 26; Authors: Technau A, Froelich K, Hagen R, Kleinsasser N Abstract Background aims. The chondrogenic differentiation potential of mesenchymal stromal cells (MSC), as well as their immunosuppressive properties, have been studied extensively. So far, only a few studies have addressed the question of whether MSC still retain their immunosuppressive qualities after transdifferentiation. In particular, the expression of immunogenic markers, such as human leukocyte antigen (HLA)-DR, after differentiation has never been investigated. Methods. Chondrogenic transdifferentiation was induced in human adipose tissue-derived stem cell (ADSC) pellet cultures derived from 10 different patients, using 10 ng/mL transforming growth factor (TGF)-beta3. Samples were harvested over a time-course of 28 days and analyzed by immunohistochemistry and reverse transcription (RT)-polymerase chain reaction (PCR). The cytokine levels in the supernatants of the samples were measured semi-quantitatively by dot-blots and quantitatively by enzyme-linked immunosorbant assays (ELISA). Results. Undifferentiated ADSC were negative for chondrogenic markers, as well as HLA-ABC and HLA-DR epitopes in immunofluorescence. In contrast, TGF-beta3-induced pellet cultures showed both expression of chondrogenic differentiation markers, such as transcription factor 9 (Sox 9), collagen type IIa and aggrecan, and an up-regulation of HLA-DR, beginning at day 7 after induction. Interferon-gamma (INF-gamma) is known to up-regulate HLA-DR. Therefore we measured INF-gamma levels in the supernatants of TGF-beta3-induced pellets and, indeed, INF-gamma was up-regulated during chondrogenesis in ADSC pellet cultures. However, both undifferentiated and TGF-beta3-induced ADSC also showed expression of immunosuppressive HLA-G and interleukin (IL)-10 up-regulation. Conclusions. These results suggest that the immunogenicity of adult stem cell-derived tissue should be tested in animal models before clinical trials for allogeneic engineered tissue are considered. PMID: 20795757 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells and the repair of radiation-induced salivary gland damage. Oral Dis. 2010 Aug 26; Authors: Coppes R, Stokman M Oral Diseases (2010) doi: 10.1111/j.1601-0825.2010.01723.x Hyposalivation underlying xerostomia after radiotherapy is still a major problem in the treatment of head and neck cancer. Stem cell therapy may provide a means to reduce radiation-induced hyposalivation and improve the quality of life of patients. This review discusses the current status in salivary gland stem cell research with respect to their potential to attenuate salivary gland dysfunction. Knowledge on the embryonic development, homeostasis and regeneration after atrophy of the salivary glands has provided important knowledge on the location of the salivary gland as well as on the factors that influence proliferation and differentiation. This knowledge has helped to locate, isolate and characterize cell populations that contain the salivary gland stem cell, although the exact tissue stem cell is still unidentified. The role that stem/progenitor cells play in the response to radiation and the factors that can influence stem/progenitor induced proliferation and differentiation are discussed. Finally, the mobilization and transplantation of stem cells and supportive cells and their potential to attenuate radiation-induced salivary gland damage are discussed. Based on the major advances made in the field of stem cell research, stem cell-based therapy has great potential to allow prevention or treatment of radiation-induced hyposalivation. PMID: 20796229 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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