Tuesday, February 2, 2010

2/3 TE-RegenMed-StemCell feed

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The Latest on Changes in CIRM's Biotech Loan Program
February 2, 2010 at 7:43 PM

CIRM today reported another change in what is to be expected concerning alterations in the $500 million biotech loan program at tomorrow's and Thursday's meetings of its board of directors. In an email, Don Gibbons, CIRM's chief communications officer, said,"There is a bit of change again in the agenda. We decided that we needed the loan term guidelines for the Early Translational RFA and that
 

Advisory
February 2, 2010 at 6:43 PM

The link in the "Fecundity" item today was faulty. It has now been fixed.
 

3-D scaffold provides clean, biodegradable structure for stem cell growth
February 2, 2010 at 6:28 PM

 

Regenocyte Successfully Treats Cardiomyopathy Patient Using His Own Adult Stem Cells
February 2, 2010 at 3:28 PM

 

UC Riverside's new state-of-the-art technology to accelerate stem cell research
February 2, 2010 at 2:28 PM

 

Stem Cell Therapy: Pieces of the Puzzle.
February 2, 2010 at 8:51 AM

Stem Cell Therapy: Pieces of the Puzzle.

J Cardiovasc Transl Res. 2010 Feb;3(1):49-60

Authors: Schoenhard JA, Hatzopoulos AK

Acute ischemic injury and chronic cardiomyopathies can cause irreversible loss of cardiac tissue leading to heart failure. Cellular therapy offers a new paradigm for treatment of heart disease. Stem cell therapies in animal models show that transplantation of various cell preparations improves ventricular function after injury. The first clinical trials in patients produced some encouraging results, despite limited evidence for the long-term survival of transplanted cells. Ongoing research at the bench and the bedside aims to compare sources of donor cells, test methods of cell delivery, improve myocardial homing, bolster cell survival, and promote cardiomyocyte differentiation. This article reviews progress toward these goals.

PMID: 20119487 [PubMed - as supplied by publisher]

 

New concepts in cardiac stem cell therapy.
February 2, 2010 at 8:51 AM

New concepts in cardiac stem cell therapy.

Hellenic J Cardiol. 2010 Jan-Feb;51(1):10-4

Authors: Wojakowski W, Tendera M

PMID: 20118038 [PubMed - in process]

 

Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis.
February 2, 2010 at 8:51 AM

Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis.

Neurosci Lett. 2010 Jan 28;

Authors: Choi MR, Kim HY, Park JY, Lee TY, Baik CS, Chai YG, Jung KH, Park KS, Roh W, Kim KS, Kim SH

Mesenchymal stem cells (MSCs) obtained from bone marrow (BM) are currently used as an alternative therapy in amyotrophic lateral sclerosis (ALS) patients. Selection of optimal passages of autologous BM-derived MSCs during long-term in vitro expansion is important for clinical trials in patients with ALS. We isolated and expanded MSCs from the BM of eight ALS patients to analyze the growth kinetics, differentiation potential, cellular surface antigen expression, karyotype modifications and secretion of various cytokines during long-term culture. The morphology and size of the cells changed from small and spindle-like cells to large and polygonal types in later passages. The growth rate of the MSCs was highest in the third passage, followed by a gradual decrease. There were no special modifications of cell surface antigens or the karyotype of the MSCs from the first to the tenth passage. MSCs in the fourth passage were differentiated into adipocytes, osteocytes and ! chondrocytes. When we analyzed the cultured media of MSCs at the third, fifth, seventh and ninth passages, IL-6, VEGF and IL-8 showed high expression, with more than 50pg/10,000 cells at these passages; however, their expression progressively decreased with additional passages. In addition, secretion of IL-15, GM-CSF, IL-10, PDGF bb, G-CSF, IL-1beta, basic FGF and IFN-gamma gradually decreased over prolonged culture. We suggest that MSCs at earlier passages are more suitable for stem cell therapy in ALS patients because of their stability and more potent anti-inflammatory and neuroprotective properties.

PMID: 20117176 [PubMed - as supplied by publisher]

 

[Progress in researches on stem cell therapy for erectile dysfunction]
February 2, 2010 at 8:51 AM

[Progress in researches on stem cell therapy for erectile dysfunction]

Zhonghua Nan Ke Xue. 2009 Oct;15(10):937-40

Authors: Jiang YB, Gou X

Erectile dysfunction (ED) commonly results from endothelial dysfunction and erectile nerve damage. Recent researches have focused on the preclinical studies of stem cell-based therapies targeted at repairing penile endothelium and protecting erectile nerves. Early studies showed that stem cell- or gene-modified stem cell-based therapies may have enduring efficacy and eventually lead to a cure for ED. Such stem cells as embryonic, mesenchymal, muscle-derived and adipose-derived ones and endothelial progenitor cells all have differentiation potentials and obvious advantages in protecting and repairing both nervi erigentes and corpus cavernosum vascular endothelial cells. Stem cell-based therapies promise to be an effective approach to human erectile dysfunction.

PMID: 20112746 [PubMed - in process]

 

Arrowhead's Portfolio Company, Nanotope, Publishes Preclinical Data Demonstrating Cartilage Regeneration
February 2, 2010 at 8:27 AM

 

Fecundity, Stem Cells and the Dark Side of Prop. 71
February 2, 2010 at 7:30 AM

Los Angeles Times columnist Michael Hiltzik has provided a bit of a filip to his look Monday at the California stem cell agency.It came in the form of an entry in his blog entitled "Of stem cells and administrative arrogance."Among other things, he said Prop. 71, which created California's $3 billion research effort, was "too specific about how the program would be managed and how it would spend
 

Effects of weak static magnetic fields on endothelial cells.
February 2, 2010 at 6:59 AM

Effects of weak static magnetic fields on endothelial cells.

Bioelectromagnetics. 2010 Jan 29;

Authors: Martino CF, Perea H, Hopfner U, Ferguson VL, Wintermantel E

Pulsed electromagnetic fields (PEMFs) have been used extensively in bone fracture repairs and wound healing. It is accepted that the induced electric field is the dose metric. The mechanisms of interaction between weak magnetic fields and biological systems present more ambiguity than that of PEMFs since weak electric currents induced by PEMFs are believed to mediate the healing process, which are absent in magnetic fields. The present study examines the response of human umbilical vein endothelial cells to weak static magnetic fields. We investigated proliferation, viability, and the expression of functional parameters such as eNOS, NO, and also gene expression of VEGF under the influence of different doses of weak magnetic fields. Applications of weak magnetic fields in tissue engineering are also discussed. Static magnetic fields may open new venues of research in the field of vascular therapies by promoting endothelial cell growth and by enhancing the healing ! response of the endothelium. Bioelectromagnetics. (c) 2010 Wiley-Liss, Inc.

PMID: 20119972 [PubMed - as supplied by publisher]

 

Array of amorphous calcium phosphate particles improves cellular activity on a hydrophobic surface.
February 2, 2010 at 6:59 AM

Array of amorphous calcium phosphate particles improves cellular activity on a hydrophobic surface.

J Biomed Mater Res B Appl Biomater. 2010 Jan 29;

Authors: Kim I, Kim HJ, Kim HM

Poor interaction between cells and surfaces, especially hydrophobic surfaces, results in delayed proliferation and increased apoptosis due to low cell adhesion signaling. To improve cell adhesion, hydrophilic array of amorphous calcium phosphate (ACP) was fabricated on a surface. A phosphate-buffered solution containing calcium ions was prepared at low temperature to prevent spontaneous precipitation. Then, the ion solution was heated to generate nuclei of ACP nanoparticles. The ACP nanoparticles adhered to the hydrophobic polystyrene surface forming an array composed of ACP particles. Multiple treatments of these nuclei with fresh CaP ion solutions increased the diameter and decreased the solubility of ACP particles enough to mediate cellular adhesion. The particle density in the array was dependent on the ion concentration of the CaP ion solutions. The ACP array improved a wide variety of activities when osteoblastic MC3T3-E1 cells were cultured on the ACP array! fabricated on a hydrophobic bacteriological dish surface, compared to those cultured without the ACP array in vitro. The use of ACP array resulted in a lower apoptosis and also increased the spreading of cells to form stress fibers and focal contacts. Cells cultured on the ACP array proliferated more than cells cultured on a hydrophobic surface without the ACP array. The ACP array increased the expression of markers of differentiation in osteoblast. These results indicate that an array of ACP can be used as a coating material for enhancing biocompatibility in tissue engineering or biomaterials rather than modifying the surface with organic molecules. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.

PMID: 20119940 [PubMed - as supplied by publisher]

 

Polysialic acid immobilized on silanized glass surfaces: a test case for its use as a biomaterial for nerve regeneration.
February 2, 2010 at 6:59 AM

Polysialic acid immobilized on silanized glass surfaces: a test case for its use as a biomaterial for nerve regeneration.

J Mater Sci Mater Med. 2010 Jan 30;

Authors: Steinhaus S, Stark Y, Bruns S, Haile Y, Scheper T, Grothe C, Behrens P

The immobilization of polysialic acid (polySia) on glass substrates has been investigated with regard to the applicability of this polysaccharide as a novel, biocompatible and bioresorbable material for tissue engineering, especially with regard to its use in nerve regeneration. PolySia, a homopolymer of alpha-2,8-linked sialic acid, is involved in post-translational modification of the neural cell adhesion molecule (NCAM). The degradation of polySia can be controlled which makes it an interesting material for coating and for scaffold construction in tissue engineering. Here, we describe the immobilization of polySia on glass surfaces via an epoxysilane linker. Whereas glass surfaces will not actually be used in nerve regeneration scaffolds, they provide a simple and efficient means for testing various methods for the investigation of immobilized polySia. The modified surfaces were investigated with contact angle measurements and the quantity of immobilized polySi! a was examined by the thiobarbituric acid assay and a specific polySia-ELISA. The interactions between the polySia-modified surface and immortalized Schwann cells were evaluated via cell adhesion and cell viability assays. The results show that polySia can be immobilized on glass surfaces via the epoxysilane linker and that surface-bound polySia has no toxic effects on Schwann cells. Therefore, as a key substance in the development of vertebrates and as a favourable substrate for the cultivation of Schwann cells, it offers interesting features for the use in nerve guidance tubes for treatment of peripheral nerve injuries.

PMID: 20119645 [PubMed - as supplied by publisher]

 

The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering.
February 2, 2010 at 6:59 AM

The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering.

Biomaterials. 2010 Jan 29;

Authors: Zreiqat H, Ramaswamy Y, Wu C, Paschalidis A, Lu Z, James B, Birke O, McDonald M, Little D, Dunstan CR

In this study we developed novel scaffolds through the controlled substitution and incorporation of strontium and zinc into a calcium-silicon system to form Sr-Hardystonite (Sr-Ca(2)ZnSi(2)O(7), Sr-HT). The physical and biological properties of Sr-HT were compared to Hardystonite (Ca(2)ZnSi(2)O(7)) [HT]. We showed that Sr-HT scaffolds are porous with interconnected porous network (interconnectivity: 99%) and large pore size (300-500mum) and an overall porosity of 78%, combined with a relatively high compressive strength (2.16+/-0.52MPa). These properties are essential for enhancing bone ingrowth in load-bearing applications. Sr-HT ceramic scaffolds induced the attachment and differentiation of human bone derived cells (HOB), compared to that for the HT scaffolds. Sr-HT scaffolds enhanced expression of alkaline phosphatase, Runx-2, osteopontin, osteocalcin and bone sialoprotein. The in vivo osteoconductivity of the scaffolds was assessed at 3 and 6 weeks following ! implantation in tibial bone defects in rats. Histological staining revealed rapid new growth of bone into the pores of the 3D scaffolds with the Sr-HT and HT, relative to the beta-tricalcium phosphate (beta-TCP). In vivo, HT and Sr-HT produced distinct differences in the patterns of degradation of the materials, and their association with TRAP positive osteoclast-like cells with HT appearing more resistant compared to both Sr-HT and beta-TCP.

PMID: 20117832 [PubMed - as supplied by publisher]

 

Carbohydrate engineered cells for regenerative medicine.
February 2, 2010 at 6:59 AM

Carbohydrate engineered cells for regenerative medicine.

Adv Drug Deliv Rev. 2010 Jan 28;

Authors: Du J, Yarema KJ

Carbohydrates are integral components of the stem cell niche on several levels; proteoglycans are a major constituent of the extracellular matrix (ECM) surrounding a cell, glycosoaminoglycans (GAGs) help link cells to the ECM and the neighboring cells, and small but informationally-rich oligosaccharides provide a "sugar code" that identifies each cell and provides it with unique functions. This article samples roles that glycans play in development and then describes how metabolic glycoengineering - a technique where monosaccharide analogs are introduced into the metabolic pathways of a cell and are biosynthetically incorporated into the glycocalyx - is overcoming many of the long-standing barriers to manipulating carbohydrates in living cells and tissues and is becoming an intriguing new tool for tissue engineering and regenerative medicine.

PMID: 20117158 [PubMed - as supplied by publisher]

 

Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation.
February 2, 2010 at 6:59 AM

Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation.

Biochem Biophys Res Commun. 2010 Jan 28;

Authors: Yu H, Tay CY, Leong WS, Tan SC, Liao K, Tan LP

Human mesenchymal stem cells (hMSCs) have gained widespread attention in the field of tissue engineering but not much is known about the changes of mechanical properties during the process of cell lineage commitment and the mechanisms of these behaviors. It is believed that exploring the inter-relations between stem cells mechanical properties and lineage commitment will shed light on the mechanobiology aspect of differentiation. hMSCs were cultured in adipogenic and osteogenic mediums and the elastic moduli were monitored using micropipette aspiration. It was found that hMSCs undergoing osteogenesis have an instantaneous Young's modulus of 890+/-219 Pa and an equilibrium Young's modulus of 224+/-40 Pa, each is about 2 fold higher than the control group. Interestingly, cells cultured in adipogenic medium exhibited a slight increase in the cellular modulus followed by a decrease relative to that of the control group. Gene expression study was employed to gain insig! hts into this phenomenon. Concomitant up regulation of actin binding filamin A (FLNa) and gamma-Tubulin with the cellular elastic modulus indicated their important role in mechanical regulation during hMSCs differentiation. Statistical results showed that cell shape and cell area changed with cellular mechanical properties, which means that cell morphology has a close relation with cell elastic modulus in the initial stage of differentiation. Collectively, these results provide a quantitative description of hMSCs mechanical behavior during the process of differentiation as well as the possible accompanying mechanism at the biomolecular level.

PMID: 20117089 [PubMed - as supplied by publisher]

 

[Principles of the local treatment: Surgical processing.]
February 2, 2010 at 6:59 AM

[Principles of the local treatment: Surgical processing.]

Pathol Biol (Paris). 2010 Jan 28;

Authors: Chaouat M, Zakine G, Mimoun M

The deep burns require a surgical treatment. The third degree circular burns require escharotomies and sometimes fasciotomies to avoid vascular compression. Early burn wound excision permits to remove the necrotic tissue that produce toxins and encourage infection. Wound coverage by an autologous split-thickness skin grafting, meshed or not, usually leads to a correct scare quality. In severe burns, when donor's sites are limited, the homografts permit to pass a cape even though they are rejected secondarily. The keratinocytes culture remains a difficult and exceptional technique for very severe burns permitting to save their life but with poor cosmetic results. Artificial dermal substitute could sometimes permit to replace the homograft and to improve the cosmetic results of the grafts by a better reconstitution of skin. If early burn wound excision with autologous split-thickness skin grafting remains the gold standard, the tissue-engineering will be a future wa! y for the surgical treatment of the burns.

PMID: 20116939 [PubMed - as supplied by publisher]

 

Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran-hyaluronic acid conjugates for cartilage tissue engineering.
February 2, 2010 at 6:59 AM

Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran-hyaluronic acid conjugates for cartilage tissue engineering.

Biomaterials. 2010 Jan 28;

Authors: Jin R, Moreira Teixeira LS, Dijkstra PJ, van Blitterswijk CA, Karperien M, Feijen J

Polysaccharide hybrids consisting of hyaluronic acid (HA) grafted with a dextran-tyramine conjugate (Dex-TA) were synthesized and investigated as injectable biomimetic hydrogels for cartilage tissue engineering. The design of these hybrids (denoted as HA-g-Dex-TA) is based on the molecular structure of proteoglycans present in the extracellular matrix of native cartilage. Hydrogels of HA-g-Dex-TA were rapidly formed within 2 min via enzymatic crosslinking of the tyramine residues in the presence of horseradish peroxidase and hydrogen peroxide. The gelation time, equilibrium swelling and storage modulus could be adjusted by varying the degree of substitution of tyramine residues and polymer concentration. Bovine chondrocytes incorporated in the HA-g-Dex-TA hydrogels remained viable, as shown by the Live-dead assay. Moreover, enhanced chondrocyte proliferation and matrix production were observed in the HA-g-Dex-TA hydrogels compared to Dex-TA hydrogels. These result! s suggest that HA-g-Dex-TA hydrogels have a high potential as injectable scaffolds for cartilage tissue engineering.

PMID: 20116847 [PubMed - as supplied by publisher]

 

Polyblend nanofibers for biomedical applications: perspectives and challenges.
February 2, 2010 at 6:59 AM

Polyblend nanofibers for biomedical applications: perspectives and challenges.

Trends Biotechnol. 2010 Jan 28;

Authors: Gunn J, Zhang M

Advances in disease treatment and tissue regeneration are buoyed by new, multifaceted materials that emulate and coercively interact with the local microenvironment. Polyblend nanofibers represent an emerging class of biomimetic nanostructures that can act as proxies of the native tissue, while providing topographical and biochemical cues that promote healing. These fibers are prepared with mixtures of synthetically and naturally derived polymers that can behave cooperatively to demonstrate unique combinations of mechanical, biochemical and structural properties. This flexibility has led to the application of polyblend nanofibers in a wide assortment of tissue engineering and drug delivery systems. In this review, we will examine design criteria and properties of polymer-blend nanofibers and their use in tissue engineering and local therapeutic delivery applications.

PMID: 20116113 [PubMed - as supplied by publisher]

 

Genetically modified cells in regenerative medicine and tissue engineering.
February 2, 2010 at 6:59 AM

Genetically modified cells in regenerative medicine and tissue engineering.

Adv Drug Deliv Rev. 2010 Jan 26;

Authors: Sheyn D, Mizrahi O, Benjamin S, Pelled G, Gazit D

Regenerative medicine appears to take as its patron, the Titan Prometheus, whose liver was able to regenerate daily, as the field attempts to restore lost, damaged, or aging cells and tissues. The tremendous technological progress achieved during the last decade in gene transfer methods and imaging techniques, as well as recent increases in our knowledge of cell biology, have opened new horizons in the field of regenerative medicine. Genetically engineered cells are a tool for tissue engineering and regenerative medicine, albeit a tool whose development is fraught with difficulties. Gene-and-cell therapy offers solutions to severe problems faced by modern medicine, but several impediments obstruct the path of such treatments as they move from the laboratory toward the clinical setting. In this review we provide an overview of recent advances in the gene-and-cell therapy approach and discuss the main hurdles and bottlenecks of this approach on its path to clinical ! trials and prospective clinical practice.

PMID: 20114067 [PubMed - as supplied by publisher]

 

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