| The Postischemic Environment Differentially Impacts Teratoma or Tumor Formation After Transplantation of Human Embryonic Stem Cell-Derived Neural Progenitors.
November 27, 2009 at 8:13 am
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| | The Postischemic Environment Differentially Impacts Teratoma or Tumor Formation After Transplantation of Human Embryonic Stem Cell-Derived Neural Progenitors. Stroke. 2009 Nov 25; Authors: Seminatore C, Polentes J, Ellman D, Kozubenko N, Itier V, Tine S, Tritschler L, Brenot M, Guidou E, Blondeau J, Lhuillier M, Bugi A, Aubry L, Jendelova P, Sykova E, Perrier AL, Finsen B, Onteniente B BACKGROUND AND PURPOSE: Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have analyzed the relative effects of the stage of differentiation and the postischemic environment on the formation of adverse structures by transplanted human embryonic stem cell-derived neural progenitors. METHODS: Four differentiation stages were identified on the basis of quantitative polymerase chain reaction expression of pluripotency, proliferation, and differentiation markers. Neural progenitors were transplanted at these 4 stages into rats with no, small, or large middle cerebral artery occlusion lesions. The fate of each transplant was compared with their pretransplantation status 1 to 4 months posttransplantation. RESULTS: The influence of the postischemic environment was limited to graft survival and occurrence of nonneuroectodermal structures after transplantation of very immature neural progenitors. Both effects were lost with differentiation. We identified a particular stage of differentiation characterized in vitro by a rebound of proliferative activity that produced highly proliferative grafts susceptible to threaten surrounding host tissues. CONCLUSIONS: The effects of the ischemic environment on the formation of teratoma by transplanted human embryonic stem cell-derived neural progenitors are limited to early differentiation stages that will likely not be used for stem cell therapy. In contrast, hyperproliferation observed at later stages of differentiation corresponds to an intrinsic activity that should be monitored to avoid tumorigenesis. PMID: 19940279 [PubMed - as supplied by publisher] |
| The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction.
November 27, 2009 at 8:13 am
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| | The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction. FASEB J. 2009 Nov 25; Authors: Adler ED, Chen VC, Bystrup A, Kaplan AD, Giovannone S, Briley-Saebo K, Young W, Kattman S, Mani V, Laflamme M, Zhu WZ, Fayad Z, Keller G We recently described a murine embryonic stem cell (ESC) line engineered to express the activated Notch 4 receptor in a tetracycline (doxcycline; Dox) regulated fashion (tet-notch4 ESCs). Notch 4 induction in Flk1(+) hematopoietic and vascular progenitors from this line respecified them to a cardiovascular fate. We reasoned that these cells would be ideal for evaluating the contribution of the cardiomyocyte and vascular lineages to the functional improvement noted following stem cell transplantation in infarcted hearts. Flk-1(+) Tet-notch4 cells from d 3 embryoid bodies exposed to doxycycline (Dox(+)) were compared to uninduced (Dox(-)) Flk-1(+) cells. Mice underwent transplantation of 5 x 10(5) Dox(+) cells, Dox(-)cells, or an equal volume of serum-free medium after surgically induced myocardial infarction. The mean ejection fraction was 59 +/- 15, 46 +/- 17, and 39 +/- 13% in the Dox(+), Dox(-), and serum-free medium groups, respectively (P<0.05 for the differences among all 3 groups). Immunohistochemistry of hearts injected with Dox(+) grafts expressed myocardial and vascular markers, whereas grafts of Dox(-) cells expressed primarily vascular markers. We conclude that cardiovascular progenitors are more effective than vascular progenitors in improving function after myocardial infarction. The transplantation of appropriate cell types is critical for maximizing the benefit of cardiovascular cell therapy.-Adler, E. D., Chen, V. C., Bystrup, A., Kaplan, A. D., Giovannone, S., Briley-Saebo, K., Young, W., Kattman, S., Mani, V., Laflamme, M., Zhu, W.-Z., Fayad, Z., Keller, G. The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction. PMID: 19940262 [PubMed - as supplied by publisher] |
| Stem cell therapy for hereditary breast cancer.
November 27, 2009 at 8:13 am
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| | Stem cell therapy for hereditary breast cancer. Tsitol Genet. 2009 May-Jun;43(3):80-8 Authors: Rassi H Both hereditary and sporadic breast cancers may develop through dysregulation of self-renewal pathways of normal mammary stem cells. Networks of proto-oncogenes and tumor suppressors that control cancer cell proliferation also regulate stem cell self-renewal and possibly stem cell aging. Breast cancer susceptibility gene (BRCA1) is a nuclear phosphoprotein expressed in many nuclear processes, including stem cell regulator, DNA damage repair, recombination, transcription, ubiquitination, cell cycle checkpoint enforcement, and centrosome regulation. In this study, we report on recent advances on the functions of embryonic, fetal, and adult stem cell progenitors for hereditary breast cancer therapies. Several molecular targeting therapies are described by activation and blocking distinct developmental signaling cascade elements, such as BRCA1, EGFR, hedgehog, Wnt/beta-catenin, and/or Notch pathways, which are frequently upregulated in cancer progenitor cells during the initiation and development of breast cancer. PMID: 19938640 [PubMed - in process] |
| Regulatory requirements for clinical trial and marketing authorisation application for cell-based medicinal products.
November 27, 2009 at 6:54 am
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| | Regulatory requirements for clinical trial and marketing authorisation application for cell-based medicinal products. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2009 Nov 27; Authors: Salmikangas P, Flory E, Reinhardt J, Hinz T, Maciulaitis R The new era of regenerative medicine has led to rapid development of new innovative therapies especially for diseases and tissue/organ defects for which traditional therapies and medicinal products have not provided satisfactory outcome. Although the clinical use and developments of cell-based medicinal products (CBMPs) could be witnessed already for a decade, robust scientific and regulatory provisions for these products have only recently been enacted. The new Regulation for Advanced Therapies (EC) 1394/2007 together with the revised Annex I, Part IV of Directive 2001/83/EC provides the new legal framework for CBMPs. The wide variety of cell-based products and the foreseen limitations (small sample sizes, short shelf life) vs. particular risks (microbiological purity, variability, immunogenicity, tumourigenicity) associated with CBMPs have called for a flexible, case-by-case regulatory approach for these products. Consequently, a risk-based approach has been developed to allow definition of the amount of scientific data needed for a Marketing Authorisation Application (MAA) of each CBMP. The article provides further insight into the initial risk evaluation, as well as to the quality, non-clinical, and clinical requirements of CBMPs. Special somatic cell therapies designed for active immunotherapy are also addressed. PMID: 19940964 [PubMed - as supplied by publisher] |
| Initiation and Progression of Axonopathy in Experimental Autoimmune Encephalomyelitis.
November 27, 2009 at 6:54 am
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| | Initiation and Progression of Axonopathy in Experimental Autoimmune Encephalomyelitis. J Neurosci. 2009 Nov 25;29(47):14965-14979 Authors: Soulika AM, Lee E, McCauley E, Miers L, Bannerman P, Pleasure D Axonal loss is the principal cause of chronic disability in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). In C57BL/6 mice with EAE induced by immunization with myelin oligodendrocyte glycoprotein peptide 35-55, the first evidences of axonal damage in spinal cord were in acute subpial and perivascular foci of infiltrating neutrophils and lymphocytes and included intra-axonal accumulations of the endovesicular Toll-like receptor TLR8, and the inflammasome protein NAcht leucine-rich repeat protein 1 (NALP1). Later in the course of this illness, focal inflammatory infiltrates disappeared from the spinal cord, but there was persistent activation of spinal cord innate immunity and progressive, bilaterally symmetric loss of small-diameter corticospinal tract axons. These results support the hypothesis that both contact-dependent and paracrine interactions of systemic inflammatory cells with axons and an innate immune-mediated neurodegenerative process contribute to axonal loss in this multiple sclerosis model. PMID: 19940192 [PubMed - as supplied by publisher] |
| Rapid detection of Acanthamoeba cysts in frozen sections of corneal scrapings with Fungiflora Y.
November 27, 2009 at 6:54 am
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| | Rapid detection of Acanthamoeba cysts in frozen sections of corneal scrapings with Fungiflora Y. Br J Ophthalmol. 2009 Dec;93(12):1563-1565 Authors: Shiraishi A, Kobayashi T, Hara Y, Yamaguchi M, Uno T, Ohashi Y AIMS: To evaluate the usefulness of serial frozen sections of corneal scrapings stained with Fungiflora Y (FFY) to diagnose Acanthamoeba keratitis (AK). METHODS: Eight patients with suspected AK were studied. Serial frozen sections were made from part of the corneal epithelial scrapings and stained with FFY. The remaining corneal epithelial scrapings were submitted for laboratory culture. RESULTS: The FFY stained frozen sections were completed within an hour, and Acanthamoeba cysts were detected under a fluorescence microscope in all eight patients. The same sections were examined with a light microscope, and Acanthamoeba cysts were confirmed to be present from their morphological characteristics. Five of the eight patients had positive laboratory cultures for Acanthamoeba. CONCLUSION: FFY staining of frozen sections of corneal scrapings is a rapid and reliable technique which can be used to make an early diagnosis of AK. PMID: 19939794 [PubMed - as supplied by publisher] |
| Biomaterials and Mesenchymal Stem Cells for Regenerative Medicine.
November 27, 2009 at 6:54 am
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| | Biomaterials and Mesenchymal Stem Cells for Regenerative Medicine. Recent Pat Biotechnol. 2009 Nov 26; Authors: Zippel N, Schulze M, Tobiasch E The reconstruction of hard and soft tissues is a major challenge in regenerative medicine, since diseases or traumas are causing increasing numbers of tissue defects due to the aging of the population. Modern tissue engineering is increasingly using three-dimensional structured biomaterials in combination with stem cells as cell source, since mature cells are often not available in sufficient amounts or quality. Biomaterial scaffolds are developed that not only serve as cell carriers providing mechanical support, but actively influence cellular responses including cell attachment and proliferation. Chemical modifications such as the incorporation of chemotactic factors or cell adhesion molecules are examined for their ability to enhance tissue development successfully. E.g. growth factors have been investigated extensively as substances able to support cell growth, differentiation and angiogenesis. Thus, continuously new patents and studies are published, which are investigating the advantages and disadvantages of different biomaterials or cell types for the regeneration of specific tissues. This review focuses on biomaterials, including natural and synthetic polymers, ceramics and corresponding composites used as scaffold materials to support cell proliferation and differentiation for hard and soft tissues regeneration. In addition, the local delivery of drugs by scaffold biomaterials is discussed. PMID: 19939237 [PubMed - as supplied by publisher] |
| Deciphering The Oligodendrogenic Program Of Neural Progenitors: Cell Intrinsic And Extrinsic Regulators.
November 27, 2009 at 6:54 am
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| | Deciphering The Oligodendrogenic Program Of Neural Progenitors: Cell Intrinsic And Extrinsic Regulators. Stem Cells Dev. 2009 Nov 25; Authors: Rivera FJ, Steffenhagen C, Kremer D, Kandasamy M, Sandner B, Couillard-Despres S, Weidner N, Kuery P, Aigner L In the developing and adult CNS, neural stem/progenitor cells (NSPCs) and oligodendroglial progenitor cells (OPCs) follow an oligodendrogenic process with the aim of myelinating axons. This process is to a high degree regulated by an oligodendrogenic program (OPr) composed of intrinsic and extrinsic factors that modulate the different steps required for NSPCs to differentiate into myelinating oligodendrocytes. Even though NSPCs and OPCs are present in the diseased CNS and have the capacity to generate oligodendrocytes, sparse re-myelination of axons constitutes a major constraint in therapies towards multiple sclerosis (MS) and spinal cord injury (SCI). Lack of pro-oligodendrogenic factors and presence of anti-oligodendrogenic activities are thought to be the main reasons for this limitation. Thus, molecular and cellular strategies aiming at re-myelination and at targeting such pro- and anti-oligodendrogenic mechanisms are currently under investigation. The present review summarizes the current knowledge on the OPr, it implements our own findings on mesenchymal, stem cell-derived pro-oligodendroglial factors and on the role of p57/kip2 in oligodendroglial differentiation. Moreover, it describes molecular and cellular approaches for the development of future therapies towards re-myelination. PMID: 19938982 [PubMed - as supplied by publisher] |
| Absence of Biglycan Accelerates the Degenerative Process in Mouse Intervertebral Disc.
November 27, 2009 at 6:15 am
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| | Absence of Biglycan Accelerates the Degenerative Process in Mouse Intervertebral Disc. Spine (Phila Pa 1976). 2009 Dec 1;34(25):E911-E917 Authors: Furukawa T, Ito K, Nuka S, Hashimoto J, Takei H, Takahara M, Ogino T, Young MF, Shinomura T STUDY DESIGN.: A study of the histologic changes of the intervertebral discs (IVDs) in biglycan (Bgn)-deficient mice. OBJECTIVE.: In this study, we investigate whether the absence of Bgn accelerates the degenerative process in mouse intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA.: Proteoglycans and collagen fibrils are major components in the extracellular matrix (ECM) composition of IVD. The ECM of IVD contains several members of the small leucine repeat proteoglycans (SLRPs) family. Bgn is one member of SLRPs family, and showed a unique expression with age and degeneration in the human IVD. To date, there have been no in vivo studies to see whether SLRPs have a role in maintaining the structural integrity of IVD. To explore the functions of Bgn in the IVD, we examined discs in Bgn-deficient mice. METHODS.: A total of 30 spine specimens were harvested from wild-type (WT) and Bgn-deficient mice. Five specimens for each genotype at 4-, 6-, and 9-month old were examined in the experiments. Histologic analysis of the IVD was performed. Histologic gradings were performed separately on nucleus pulposus, anulus fibrosus, and endplate according to the classification system proposed by Boos et al. RESULTS.: We found that Bgn-deficient mice developed an early onset of disc degeneration compared with WT mice. The degenerative scores of Bgn-deficient mice were significantly higher than those of WT mice at 4- and 9-month-old. High scores for nucleus pulposus and anulus fibrosus in Bgn-deficient mice significantly affected the difference in total degenerative scores at 9 months of age. CONCLUSION.: Bgn deficiency significantly accelerated disc degeneration. PMID: 19940720 [PubMed - as supplied by publisher] |
| Effects of Extracellular Matrix on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Smooth Muscle Cell Lineage: Utility for Cardiovascular Tissue Engineering.
November 27, 2009 at 6:15 am
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| | Effects of Extracellular Matrix on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Smooth Muscle Cell Lineage: Utility for Cardiovascular Tissue Engineering. Cells Tissues Organs. 2009 Nov 19; Authors: Suzuki S, Narita Y, Yamawaki A, Murase Y, Satake M, Mutsuga M, Okamoto H, Kagami H, Ueda M, Ueda Y Background: Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into various types of cell, and the extracellular matrix (ECM) is acknowledged to be important for the regulation of cell functions. In this study, we demonstrated the effects of ECMs on the differentiation of human bone marrow-derived MSCs into a smooth muscle cell (SMC) lineage. Methods: Human MSCs (hMSCs) were cultured on dishes coated with 3 types of ECM including laminin (LM), collagen type IV (Col-IV) and fibronectin for 7 days, and simultaneously cultured on a noncoated dish as a control. Cell numbers of these cultured hMSCs were counted, and their expression of SMC-specific genes and proteins was evaluated. hMSCs were then seeded on LM-coated biodegradable sheets and implanted into rat subcutaneous space. After 2 weeks of implantation, these tissues were evaluated. Results: The number of hMSCs was significantly increased by culture on Col-IV-coated dishes. The expression of SMC-specific genes and proteins (alpha-smooth muscle actin, ASMA; h1-calponin, CALP) in hMSC was significantly upregulated from culture on LM-coated dishes. LM-coated sheets showed a significantly increased expression of ASMA and CALP protein in vivo. Moreover, a fully differentiated marker (SM2) was expressed in the in vivo implanted hMSCs in the course of 2 weeks on the LM-coated sheet. Conclusion: These results suggest that the signal transduction of the cell-matrix interaction for the differentiation of hMSCs into SMCs was activated when cultured with LM. LM-coated materials may thus be useful for cardiovascular tissue engineering. PMID: 19940434 [PubMed - as supplied by publisher] |
| The differential effects of hypoxia on the osteo-chondrogenic potential of human adipose-derived stem cells.
November 27, 2009 at 6:15 am
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| | The differential effects of hypoxia on the osteo-chondrogenic potential of human adipose-derived stem cells. Am J Physiol Cell Physiol. 2009 Nov 25; Authors: Merceron C, Vinatier C, Portron S, Masson M, Amiaud J, Guigand L, Cherel Y, Weiss P, Guicheux J Human adipose tissue-derived stem cells (hATSC) have been contemplated as reparative cells for cartilage engineering. Chondrogenic differentiation of hATSC can be induced by an enriched culture medium and a three dimensional environment. Given that bone is vascularized and cartilage not, oxygen tension has been suggested as a regulatory factor for osteo-chondrogenic differentiation. Our work aimed at determining whether hypoxia affects the osteo-chondrogenic potential of hATSC. HATSC were cultured in chondrogenic or osteogenic medium for 28 days, in pellets or monolayers, and under 5% or 20% oxygen tension. Cell differentiation was monitored by real-time PCR (COL2A1, aggrecan, Runx2 and osteocalcin). The chondrogenic differentiation was further evaluated by Alcian Blue and immunohistological staining for glycosaminoglycans (GAG) and type II collagen respectively. The osteogenic differentiation was also assessed by the staining of mineralized matrix (alizarin red) and measurement of alkaline phosphatase activity (ALP). The expression of chondrogenic markers was up-regulated when hATSC were exposed to hypoxia in chondrogenic medium. Conversely, osteocalcin expression, mineralization and ALP activity were severely reduced under hypoxic condition even in the presence of osteogenic medium. Our data strongly suggest that hypoxia favors the chondrogenic differentiation of hATSC as evidenced by the expression of the chondrogenic markers, whereas it could alter their osteogenic potential. Our results highlight the differential regulatory role of hypoxia on the chondrogenic and osteogenic differentiation process of hATSC. These data could help us exploit the potential of tissue engineering and stem cells to replace or restore the function of osteoarticular tissues. PMID: 19940068 [PubMed - as supplied by publisher] |
| Self-assembly of N-maleoylchitosan in aqueous media.
November 27, 2009 at 6:15 am
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| | Self-assembly of N-maleoylchitosan in aqueous media. Colloids Surf B Biointerfaces. 2009 Oct 30; Authors: Zhu A, Lu Y, Pan Y, Dai S, Wu H N-maleoylchitosan (NMCS) is a biocompatible derivative of chitosan, but its solubility in water is dependent on the degree of maleoyl substitution. In this study, the NMCS sample with a maleoyl substitution degree of 70% was synthesized by the reaction of maleic anhydride and the amino groups of chitosan. The resulting NMCS can be ready to dissolve in water over a wide pH range (from 2 to 9). The aggregation behavior of NMCS in aqueous media was studied by steady-state fluorescence spectroscopy, viscometric, field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM). The critical aggregation concentration (CAC) of NMCS in water is found to be 0.05-0.06mg/mL. With increasing NMCS concentration to approximately 0.5mg/mL, which is 10 times of the CAC, NMCS molecules self-assemble to fiber-like aggregates with an averaged diameter of approximately 2.5mum and length of more than 100mum. The driving force for the aggregation is attributed to the hydrophobic interaction as evident from isothermal titration calorimetry (ITC) study. These fiber-like aggregates might have potential applications in tissue engineering scaffold. PMID: 19939640 [PubMed - as supplied by publisher] |
| A prediction of cell differentiation and proliferation within a collagen-glycosaminoglycan scaffold subjected to mechanical strain and perfusive fluid flow.
November 27, 2009 at 6:15 am
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| | A prediction of cell differentiation and proliferation within a collagen-glycosaminoglycan scaffold subjected to mechanical strain and perfusive fluid flow. J Biomech. 2009 Nov 23; Authors: Stops AJ, Heraty KB, Browne M, O'Brien FJ, McHugh PE Mesenchymal stem cell (MSC) differentiation can be influenced by biophysical stimuli imparted by the host scaffold. Yet, causal relationships linking scaffold strain magnitudes and inlet fluid velocities to specific cell responses are thus far underdeveloped. This investigation attempted to simulate cell responses in a collagen-glycosaminoglycan (CG) scaffold within a bioreactor. CG scaffold deformation was simulated using mu-computed tomography (CT) and an in-house finite element solver (FEEBE/linear). Similarly, the internal fluid velocities were simulated using the afore-mentioned muCT dataset with a computational fluid dynamics solver (ANSYS/CFX). From the ensuing cell-level mechanics, albeit octahedral shear strain or fluid velocity, the proliferation and differentiation of the representative cells were predicted from deterministic functions. Cell proliferation patterns concurred with previous experiments. MSC differentiation was dependent on the level of CG scaffold strain and the inlet fluid velocity. Furthermore, MSC differentiation patterns indicated that specific combinations of scaffold strains and inlet fluid flows cause phenotype assemblies dominated by single cell types. Further to typical laboratory procedures, this predictive methodology demonstrated loading-specific differentiation lineages and proliferation patterns. It is hoped these results will enhance in-vitro tissue engineering procedures by providing a platform from which the scaffold loading applications can be tailored to suit the desired tissue. PMID: 19939388 [PubMed - as supplied by publisher] |
| Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration.
November 27, 2009 at 6:15 am
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| | Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration. J Biomed Sci. 2009 Nov 25;16(1):108 Authors: Subramanian A, Krishnan UM, Sethuraman S ABSTRACT: Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves. PMID: 19939265 [PubMed - as supplied by publisher] |
| Biomaterials and Mesenchymal Stem Cells for Regenerative Medicine.
November 27, 2009 at 6:15 am
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| | Biomaterials and Mesenchymal Stem Cells for Regenerative Medicine. Recent Pat Biotechnol. 2009 Nov 26; Authors: Zippel N, Schulze M, Tobiasch E The reconstruction of hard and soft tissues is a major challenge in regenerative medicine, since diseases or traumas are causing increasing numbers of tissue defects due to the aging of the population. Modern tissue engineering is increasingly using three-dimensional structured biomaterials in combination with stem cells as cell source, since mature cells are often not available in sufficient amounts or quality. Biomaterial scaffolds are developed that not only serve as cell carriers providing mechanical support, but actively influence cellular responses including cell attachment and proliferation. Chemical modifications such as the incorporation of chemotactic factors or cell adhesion molecules are examined for their ability to enhance tissue development successfully. E.g. growth factors have been investigated extensively as substances able to support cell growth, differentiation and angiogenesis. Thus, continuously new patents and studies are published, which are investigating the advantages and disadvantages of different biomaterials or cell types for the regeneration of specific tissues. This review focuses on biomaterials, including natural and synthetic polymers, ceramics and corresponding composites used as scaffold materials to support cell proliferation and differentiation for hard and soft tissues regeneration. In addition, the local delivery of drugs by scaffold biomaterials is discussed. PMID: 19939237 [PubMed - as supplied by publisher] |
| Normal human epithelial cells regulate the size and morphology of tissue-engineered capillaries.
November 27, 2009 at 6:15 am
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| | Normal human epithelial cells regulate the size and morphology of tissue-engineered capillaries. Tissue Eng Part A. 2009 Nov 25; Authors: Rochon MH, Fradette J, Fortin V, Tomasetig F, Roberge C, Baker K, Berthod F, Auger FA, Germain L The survival of thick tissues/organs produced by tissue engineering requires rapid revascularization after grafting. Although capillary-like structures have been reconstituted in some engineered tissues, little is known about the interaction between normal epithelial cells and endothelial cells involved in the in vitro angiogenic process. In the present study, we used the self-assembly approach of tissue engineering to examine this relationship. An endothelialized tissue-engineered dermal substitute (ETED) was produced by adding endothelial cells to the tissue-engineered dermal substitute (TED) produced by the self-assembly approach. The latter consists in culturing fibroblasts in medium supplemented with serum and ascorbic acid. A network of tissue-engineered capillaries (TECs) formed within the human extracellular matrix produced by dermal fibroblasts. To determine whether epithelial cells modify TECs, the size and form of TECs were studied in ETED cultured in the presence or absence of epithelial cells. In the presence of normal keratinocytes from skin, cornea or uterine cervix, endothelial cells formed small TECs (cross sectional area estimated at less than 50 mum2) reminiscent of capillaries found in the skin's microcirculation. In contrast, TECs grown in the absence of epithelial cells presented variable sizes (larger than 50 mum2), but the addition of keratinocyte-conditioned media or exogenous vascular endothelial growth factor (VEGF) induced their normalization towards a smaller size. VEGF neutralization inhibited the effect of keratinocyte-conditioned media. These results provide new direct evidence that normal human epithelial cells play a role in the regulation of the underlying TEC network, and advance our knowledge in tissue engineering for the production of tissue-engineered capillary networks in vitro. PMID: 19938961 [PubMed - as supplied by publisher] |
| Influence of Amide versus Ester Linkages on the Properties of Eight-Armed PEG-PLA Star Block Copolymer Hydrogels.
November 27, 2009 at 6:15 am
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| | Influence of Amide versus Ester Linkages on the Properties of Eight-Armed PEG-PLA Star Block Copolymer Hydrogels. Biomacromolecules. 2009 Nov 25; Authors: Buwalda SJ, Dijkstra PJ, Calucci L, Forte C, Feijen J Water-soluble eight-armed poly(ethylene glycol)-poly(l-lactide) star block copolymers linked by an amide or ester group between the PEG core and the PLA blocks (PEG-(NHCO)-(PLA)(8) and PEG-(OCO)-(PLA)(8)) were synthesized by the stannous octoate catalyzed ring-opening polymerization of l-lactide using an amine- or hydroxyl-terminated eight-armed star PEG. At concentrations above the critical gel concentration, thermosensitive hydrogels were obtained, showing a reversible single gel-to-sol transition. At similar composition PEG-(NHCO)-(PLA)(8) hydrogels were formed at significantly lower polymer concentrations and had higher storage moduli. Whereas the hydrolytic degradation/dissolution of the PEG-(OCO)-(PLA)(8) takes place by preferential hydrolysis of the ester bond between the PEG and PLA block, the PEG-(NHCO)-(PLA)(8) hydrogels degrade through hydrolysis of ester bonds in the PLA main chain. Because of their relatively good mechanical properties and slow degradation in vitro, PEG-(NHCO)-(PLA)(8) hydrogels are interesting materials for biomedical applications such as controlled drug delivery systems and matrices for tissue engineering. PMID: 19938809 [PubMed - as supplied by publisher] | | | 
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