|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Fuz Controls the Morphogenesis and Differentiation of Hair Follicles through the Formation of Primary Cilia. J Invest Dermatol. 2010 Oct 21; Authors: Dai D, Zhu H, Wlodarczyk B, Zhang L, Li L, Li AG, Finnell RH, Roop DR, Chen J Planar cell polarity (PCP) signaling is essential in determining the polarity of cells within the plane of an epithelial sheet. Core PCP genes have been recently shown to control the global polarization of hair follicles in mice. Fuz, a homologue of the Drosophila PCP effector gene, fuzzy, is critical in ciliogenesis in vertebrates, and is required for the development of a wide range of organs in mice. Here, we report that disruption of the Fuz gene in mice severely blocked the development of hair follicles in the skin. In contrast to the loss of hair follicle polarization in mice deficient in core PCP genes, hair follicles in mice lacking the Fuz gene retained their typical anterior-posterior orientation. We show that disruption of Fuz impaired the formation of primary cilia and the hedgehog signaling pathway in the skin. In addition, using skin grafts and skin reconstitution assays we demonstrate that the expression of Fuz is required in both epidermal and dermal cells and that the formation of primary cilia is a cell-autonomous process that does not require cross talk between the epithelia and mesenchymal compartments during hair follicle formation.Journal of Investigative Dermatology advance online publication, 21 October 2010; doi:10.1038/jid.2010.306. PMID: 20962855 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Differential Contribution of Dermal Resident and Bone Marrow-Derived Cells to Collagen Production during Wound Healing and Fibrogenesis in Mice. J Invest Dermatol. 2010 Oct 21; Authors: Higashiyama R, Nakao S, Shibusawa Y, Ishikawa O, Moro T, Mikami K, Fukumitsu H, Ueda Y, Minakawa K, Tabata Y, Bou-Gharios G, Inagaki Y Recent studies show that bone marrow (BM)-derived cells migrating into a dermal wound promote healing by producing collagen type I. However, their contribution to the repair process has not been fully verified yet. It is also unclear whether BM-derived cells participate in dermal fibrogenesis. We have addressed these issues using transgenic mice that harbor tissue-specific enhancer/promoter sequences of α2(I) collagen gene linked to either enhanced green fluorescent protein (COL/EGFP) or the luciferase (COL/LUC) reporter gene. Following dermal excision or subcutaneous bleomycin administration, a large number of EGFP-positive collagen-producing cells appeared in the dermis of COL/EGFP reporter mice. When wild-type mice were transplanted with BM cells from transgenic COL/EGFP animals and subjected to dermal excision, no EGFP-positive BM-derived collagen-producing cells were detected throughout the repair process. Luciferase assays of dermal tissues from COL/LUC recipient mice also excluded collagen production by BM-derived cells during dermal excision healing. In contrast, a limited but significant number of CD45-positive collagen-producing cells migrated from BM following bleomycin injection. These results indicate that resident cells in the skin are the major source of de novo collagen deposition in both physiological and pathological conditions, whereas BM-derived cells participate, in part, in collagen production during dermal fibrogenesis.Journal of Investigative Dermatology advance online publication, 21 October 2010; doi:10.1038/jid.2010.314. PMID: 20962852 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem-cell "hype" in tracheal transplantation? A response. Transplantation. 2010 Oct 27;90(8):928-9 Authors: Macchiarini P, Birchall M PMID: 20962609 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Fibronectin-mediated upregulation of α5β1 integrin and cell adhesion during differentiation of mouse embryonic stem cells. Cell Adh Migr. 2011 Jan 21;5(1) Authors: Pimton P, Sarkar S, Sheth N, Perets A, Marcinkiewicz C, Lazarovici P, Lelkes PI Embryonic stem (ES) cells have a broad potential application in regenerative medicine and can be differentiated into cells of all three germ layers. Adhesion of ES cells to extracellular matrix (ECM) proteins is essential for the differentiation pathway; Cell-ECM adhesion is mediated by integrins that have the ability to activate many intracellular signaling pathways. Therefore, we hypothesize that the expression and function of integrin receptors is a critical step in ES differentiation. Using functional cell adhesion assays, our study demonstrates that α5β1 is a major functional integrin receptor expressed on the cell surface of undifferentiated mouse ES-D3 cells, which showed significantly higher binding to fibronectin as compared to collagens. This adhesion was specific mediated by integrin α5β1 as evident from the inhibition with a disintegrin selective for this particular integrin. Differentiation of ES-D3 cells on fibronectin or on a collagen type1/fibronectin matrix, caused further selective upregulation of the α5β1 integrin. Differentiation of the cells, as evaluated by immunofluorescence, FACS analysis and quantitative RT-PCR, was accompanied by the upregulation of mesenchymal (Flk1, isolectin B4, α-SMA, vimentin) and endodermal markers (FoxA2, SOX 17, cytokeratin) in parallel to increased expression of α5β1 integrin. Taken together, the data indicate that fibronectin-mediated, upregulation of α5β1 integrin and adhesion of ES-D3 cells to specific ECM molecules are linked to early stages of mouse embryonic stem cells commitment to meso-endodermal differentiation. PMID: 20962574 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Engineering a Collagen Matrix that Replicates the Biological Properties of Native Extracellular Matrix. J Biomater Sci Polym Ed. 2010 Oct 19; Authors: Nam K, Sakai Y, Funamoto S, Kimura T, Kishida A In this study, we aimed to replicate the function of native tissues that can be used in tissue engineering and regenerative medicine. The key to such replication is the preparation of an artificial collagen matrix that possesses a structure resembling that of the extracellular matrix. We, therefore, prepared a collagen matrix by fibrillogenesis in a NaCl/Na(2)HPO(4) aqueous solution using a dialysis cassette and investigated its biological behavior in vitro and in vivo. The in vitro cell adhesion and proliferation did not show any significant differences. The degradation rate in the living body could be controlled according to the preparation condition, where the collagen matrix with high water content (F-collagen matrix, >98%) showed fast degradation and collagen matrix with lower water content (T-collagen matrix, >80%) showed no degradation for 8 weeks. The degradation did not affect the inflammatory response at all and relatively faster wound healing response was observed. Comparing this result with that of collagen gel and decellularized cornea, it can be concluded that the structural factor is very important and no cell abnormal behavior would be observed for quaternary structured collagen matrix. PMID: 20961498 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Advantages and applications of human artificial chromosome vector]. Seikagaku. 2010 Sep;82(9):846-52 Authors: Yamaguchi S, Ohbayashi T, Kazuki Y, Oshimura M PMID: 20960922 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [HGF levels in serum, cerebrospinal fluid, joint fluid, tissues and various diseases]. Nippon Rinsho. 2010 Jul;68 Suppl 7:121-30 Authors: Noma S, Funakoshi H, Nakamura T PMID: 20960760 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Mechanism of renal tubular regeneration in acute kidney injury]. Nippon Jinzo Gakkai Shi. 2010;52(5):558-61 Authors: Terada Y, Ueda S, Shimamura Y, Ogata K, Inoue K PMID: 20715586 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng. 2010 Aug 15;12:87-117 Authors: Parekkadan B, Milwid JM Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics. PMID: 20415588 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency's latest grants – more than $70 million – drew scant attention in the media this morning.
Most of the coverage was a routine rehash of the CIRM news release. Here are links to the various stories that surfaced today: Keith Darcé of the San Diego Union-Tribune, Ron Leuty of the San Francisco Business Times, Richard Halstead of the Marin Independent Journal, | | | | | | | | | | | | | | | | | | | | | | | | | Photodynamic action of Tri-meso (N-methyl-pyridyl), meso (N-tetradecyl-pyridyl) porphine on Staphylococcus epidermidis biofilms grown on Ti6Al4V alloy. Int J Artif Organs. 2010 Oct 21;33(9):636-45 Authors: Saino E, Sbarra MS, Arciola CR, Scavone M, Bloise N, Nikolov P, Ricchelli F, Visai L Staphylococcus epidermidis is a leading cause of nosocomial infections, and its virulence is attributable to formation of biofilm, especially on implanted devices. Photodynamic treatment (PDT) has been actively investigated for the eradication of bacterial biofilm growing on dental plaques and oral implants. In this study, we used Tri-meso (N-methyl-pyridyl), meso (N-tetradecyl-pyridyl) porphine (C14) for inactivation of two structurally distinct S. epidermidis biofilms grown on Ti6Al4V alloy and compared its photosensitizing efficiency with that of the parent molecule, tetra-substituted N-methyl-pyridyl-porphine (C1). A more significant reduction in bacterial survival was observed when both bacterial biofilms were exposed to a lower dose of C14, and simultaneously to visible light in comparison with C1. The different responses of both staphylococcal biofilms to C1- or C14-treatment appeared to depend on photosensitizer endocellular concentration. C14 bound to both biofilms to a greater extent than C1. Moreover, C14 penetrates deeper into the bacterial membranes, as determined by fluorescence quenching experiments with methylviologen, allowing for better bacterial killing photoefficiency. Confocal laser scanning microscope (CLSM) analysis indicated damage to bacterial cell membranes in both photodynamically treated biofilms, while disruption of PDT-treated biofilm was confirmed by scanning electron microscopy (SEM). In summary, C14 may be a potential photosensitizer for the inactivation of staphylococcal biofilms for many device-related infections which are accessible to visible light. PMID: 20963728 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Engineering a Collagen Matrix that Replicates the Biological Properties of Native Extracellular Matrix. J Biomater Sci Polym Ed. 2010 Oct 19; Authors: Nam K, Sakai Y, Funamoto S, Kimura T, Kishida A In this study, we aimed to replicate the function of native tissues that can be used in tissue engineering and regenerative medicine. The key to such replication is the preparation of an artificial collagen matrix that possesses a structure resembling that of the extracellular matrix. We, therefore, prepared a collagen matrix by fibrillogenesis in a NaCl/Na(2)HPO(4) aqueous solution using a dialysis cassette and investigated its biological behavior in vitro and in vivo. The in vitro cell adhesion and proliferation did not show any significant differences. The degradation rate in the living body could be controlled according to the preparation condition, where the collagen matrix with high water content (F-collagen matrix, >98%) showed fast degradation and collagen matrix with lower water content (T-collagen matrix, >80%) showed no degradation for 8 weeks. The degradation did not affect the inflammatory response at all and relatively faster wound healing response was observed. Comparing this result with that of collagen gel and decellularized cornea, it can be concluded that the structural factor is very important and no cell abnormal behavior would be observed for quaternary structured collagen matrix. PMID: 20961498 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Sustained Release of VEGF by Coaxial Electrospun Dextran/PLGA Fibrous Membranes in Vascular Tissue Engineering. J Biomater Sci Polym Ed. 2010 Oct 19; Authors: Jia X, Zhao C, Li P, Zhang H, Huang Y, Li H, Fan J, Feng W, Yuan X, Fan Y VEGF-loaded core/shell fibrous membranes were prepared by coaxial electrospinning with dextran (DEX) as the core component and poly(lactide-co-glycolide) (PLGA) as the shell polymer, respectively. The electrospun DEX/PLGA fibers were observed by scanning electron microscopy, transmission electron microscopy and confocal microscopy to identify the core/shell fiber structure and the protein distribution. The results of tensile tests showed that the DEX/PLGA membranes possessed lower tensile strength and higher Young's modulus than PLGA one. The release profiles demonstrated that vascular endothelial growth factor (VEGF) release sustained for more than 28 days. Studies on cell viability and spreading demonstrated that the DEX(VEGF)/PLGA membranes positively promoted cell proliferation and cell-membrane interaction, which further testified that the processed VEGF remained bioactivities. Furthermore, the detections for the up-regulation of intercellular adhesion molecular-1 and the release of von Willebrand factor under pathological stimuli, which are related to inflammation process and thrombus formation, exhibited a normal immune response for the DEX(VEGF)/PLGA membrane. These data suggested that the VEGF-loaded fibers could be feasible in vascular tissue engineering. PMID: 20961491 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Conformational Flexibility of Chitosan: A Molecular Modeling Study. Biomacromolecules. 2010 Oct 20; Authors: Skovstrup S, Hansen SG, Skrydstrup T, Schiøtt B Chitin and chitosan are naturally occurring polysaccharides composed of β-(1,4) linked N-acetylglucosamine units (GlcNAc) and, for chitosan, also glucosamine units (GlcN). In recent years, chitosan has attracted much interest because of its special physical and chemical properties related to drug delivery, wound healing, and tissue engineering. However, limited structural knowledge is available for chitosan because of its composition of the randomly mixed building blocks, GlcNAc and GlcN. In this study, we present exhaustive combined molecular dynamics and Monte Carlo simulations that unravel the conformational flexibility of the β-(1,4)-linkage in di-, tri-, and tetrasaccharide models of chitin and chitosan. The most flexible disaccharide unit was found to be GlcN-GlcNAc, populating four conformations. Furthermore, it is found that the conformational freedom of a glycosidic bond is independent of the flexibility of the neighboring linkages along the oligomer. The results are interpreted with respect to hydrogen bond formation and implications for polymer properties. PMID: 20961133 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chest wall repair with engineered fetal bone grafts: an efficacy analysis in an autologous leporine model. J Pediatr Surg. 2010 Jun;45(6):1354-60 Authors: Klein JD, Turner CG, Ahmed A, Steigman SA, Zurakowski D, Fauza DO PURPOSE: We sought to compare the efficacy of engineered fetal bone grafts with acellular constructs in an autologous model of chest wall repair. METHODS: Rabbits (n = 10) with a full-thickness sternal defect were equally divided in 2 groups based on how the defect was repaired, namely, either with an autologous bone construct engineered with amniotic mesenchymal stem cells on a nanofibrous scaffold or a size-matched identical scaffold with no cells. Animals were killed at comparable time-points 18 to 20 weeks postimplantation for multiple analyses. RESULTS: Gross evidence of nonunion confirmed by micro-computed tomography scanning was present in 3 (60%) of 5 of the acellular implants but in no engineered grafts. Histology confirmed the presence of bone in both types of repair, albeit seemingly less robust in the acellular grafts. Mineral density in vivo was significantly higher in engineered grafts than in acellular ones, with more variability among the latter. There was no difference in alkaline phosphatase activity between the groups. CONCLUSIONS: Chest wall repair with an autologous osseous graft engineered with amniotic mesenchymal stem cells leads to improved and more consistent outcomes in the midterm when compared with an equivalent acellular prosthetic repair in a leporine model. Amniotic fluid-derived engineered bone may become a practical alternative for perinatal chest wall reconstruction. PMID: 20620344 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue-engineered vascular grafts: does cell seeding matter? J Pediatr Surg. 2010 Jun;45(6):1299-305 Authors: Mirensky TL, Hibino N, Sawh-Martinez RF, Yi T, Villalona G, Shinoka T, Breuer CK PURPOSE: Use of tissue-engineered vascular grafts (TEVGs) in the repair of congenital heart defects provides growth and remodeling potential. Little is known about the mechanisms involved in neovessel formation. We sought to define the role of seeded monocytes derived from bone marrow mononuclear cells (BM-MNCs) on neovessel formation. METHODS: Small diameter biodegradable tubular scaffolds were constructed. Scaffolds were seeded with the entire population of BM-MNC (n = 15), BM-MNC excluding monocytes (n = 15), or only monocytes (n = 15) and implanted as infrarenal inferior vena cava (IVC) interposition grafts into severe combined immunodeficiency/bg mice. Grafts were evaluated at 1 week, 10 weeks, or 6 months via ultrasonography and microcomputed tomography, as well as by histologic and immunohistochemical techniques. RESULTS: All grafts remained patent without stenosis or aneurysm formation. Neovessels contained a luminal endothelial lining surrounded by concentric smooth muscle cell layer and collagen similar to that seen in the native mouse IVC. Graft diameters differed significantly between those scaffolds seeded with only monocytes (1.022 +/- 0.155 mm) and those seeded without monocytes (0.771 +/- 0.121 mm; P = .021) at 6 months. CONCLUSIONS: Monocytes may play a role in maintaining graft patency. Incorporation of such findings into the development of second-generation TEVGs will promote graft patency and success. PMID: 20620335 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cervical motion preservation using mesenchymal progenitor cells and pentosan polysulfate, a novel chondrogenic agent: preliminary study in an ovine model. Neurosurg Focus. 2010 Jun;28(6):E4 Authors: Goldschlager T, Ghosh P, Zannettino A, Gronthos S, Rosenfeld JV, Itescu S, Jenkin G OBJECT: There is an unmet need for a procedure that could generate a biological disc substitute while at the same time preserving the normal surgical practice of achieving anterior cervical decompression. The objective of the present study was to test the hypothesis that adult allogeneic mesenchymal progenitor cells (MPCs) formulated with a chondrogenic agent could synthesize a cartilaginous matrix when implanted into a biodegradable carrier and cage, and over time, might serve as a dynamic interbody spacer following anterior cervical discectomy (ACD). METHODS: Eighteen ewes were divided randomly into 3 groups of 6 animals. Each animal was subjected to C3-4 and C4-5 ACD followed by implantation of bioresorbable interbody cages and graft containment plates. The cage was packed with 1 of 3 implants. In Group A, the implant was Gelfoam sponge only. In Group B, the implant consisted of Gelfoam sponge with 1 million MPCs only. In Group C, the implant was Gelfoam sponge with 1 million MPCs formulated with the chondrogenic agent pentosan polysulfate (PPS). In each animal the cartilaginous endplates were retained intact at 1 level, and perforated in a standardized manner at the other level. Allogeneic ovine MPCs were derived from a single batch of immunoselected and culture-expanded MPCs isolated from bone marrow of outbred sheep (mixed stock). Radiological and histological measures were used to assess cartilage formation and the presence or absence of new bone formation. RESULTS: The MPCs with or without PPS were safe and well-tolerated in the ovine cervical spine. There was no significant difference between groups in the radiographic or histological outcome measures, regardless of whether endplates were perforated or retained intact. According to CT scans obtained at 3 months after the operation, new bone formation within the interbody space was observed in the Gelfoam only group (Group A) in 9 (75%) of 12 interbody spaces, and 11 (92%) of 12 animals in the MPC cohort (Group B) had new bone formation within the interbody space. Significantly, in the MPC & PPS group (Group C), there were only 1 (8%) of 12 levels with new bone formation (p = 0.0009 vs Group A; p = 0.0001 vs Group B). According to histological results, there was significantly more cartilaginous tissue within the interbody cages of Group C (MPC & PPS) compared with both the control group (Group A; p = 0.003) and the MPC Group (p = 0.017). CONCLUSIONS: This study demonstrated the feasibility of using MPCs in combination with PPS to produce cartilaginous tissue to replace the intervertebral disc following ACD. This biological approach may offer a means preserving spinal motion and offers an alternative to fusion to artificial prostheses. PMID: 20521963 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces. Biomaterials. 2010 Aug;31(23):5945-52 Authors: Park CH, Rios HF, Jin Q, Bland ME, Flanagan CL, Hollister SJ, Giannobile WV A major clinical challenge in the reconstruction of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth-supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. Here, we demonstrate multi-scale computational design and fabrication of composite hybrid polymeric scaffolds for targeted cell transplantation of genetically modified human cells for the formation of human tooth dentin-ligament-bone complexes in vivo. The newly-formed tissues demonstrate the interfacial generation of parallel- and obliquely-oriented fibers that grow and traverse within the polycaprolactone (PCL)-poly(glycolic acid) (PGA) designed constructs forming tooth cementum-like tissue, ligament, and bone structures. This approach offers potential for the clinical implementation of customized periodontal scaffolds that may enable regeneration of multi-tissue interfaces required for oral, dental and craniofacial engineering applications. PMID: 20471083 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng. 2010 Aug 15;12:87-117 Authors: Parekkadan B, Milwid JM Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics. PMID: 20415588 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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