Monday, January 31, 2011

1/31 TE-RegenMed-StemCell feed

     
    TE-RegenMed-StemCell feed    
   
California Stem Cell Agency Already Has Posted Some Statements of Economic Interests
January 31, 2011 at 12:34 PM
 
The California stem cell agency was Johnny-on-the-spot last week when its directors approved posting statements of economic interest on the CIRM web site.

Moments after the vote, Don Gibbons, chief communications officer for the agency, emailed the California Stem Cell Report, pointing out that the statements of the top executives were already up. They can found at this location or by searching
   
   
Origin and hierarchy of basal lamina-forming and -non-forming myogenic cells in mouse skeletal muscle in relation to adhesive capacity and Pax7 expression in vitro.
January 29, 2011 at 10:09 AM
 

Origin and hierarchy of basal lamina-forming and -non-forming myogenic cells in mouse skeletal muscle in relation to adhesive capacity and Pax7 expression in vitro.

Cell Tissue Res. 2011 Jan 29;

Authors: Tamaki T, Tono K, Uchiyama Y, Okada Y, Masuda M, Soeda S, Nitta M, Akatsuka A

As a novel approach to distinguish skeletal myogenic cell populations, basal lamina (BL) formation of myogenic cells was examined in the mouse compensatory enlarged plantaris muscles in vivo and in fiber-bundle cultures in vitro. MyoD(+) myogenic cells located inside the regenerative muscle fiber BL were laminin(-) but interstitial MyoD(+) cells were laminin(+). This was also confirmed by electron microscopy as structural BL formation. Similar trends were observed in the fiber-bundle cultures including satellite cells and interstitial myogenic cells and laminin(+) myogenic cells predominantly showed non-adhesive (non-Ad) behavior with Pax7(-), whereas laminin(-) cells were adhesive (Ad) with Pax7(+). Moreover, non-Ad/laminin(+) and Ad/laminin(-) myotubes were also observed and the former type showed spontaneous contractions, while the latter type did not. The origin and hierarchy of Ad/Pax7(+)/laminin(-) and non-Ad/Pax7(-)/laminin(+) myogenic cells were also examined using skeletal muscle interstitium-derived CD34(+)/45(-) (Sk-34) and CD34(-)/45(-) (Sk-DN) multipotent stem cells, which were composed of non-committed myogenic cells with a few (<1%) Pax7(+) cells in the Sk-DN cells at fresh isolation. Both cell types were separated by Ad/non-Ad capacity in repetitive culture. As expected, both Ad/Pax7(+)/laminin(-) and non-Ad/Pax7(-)/laminin(+) myogenic cells consistently appeared in the Ad and non-Ad cell culture. However, Ad/Pax7(+)/laminin(-) cells were repeatedly detected in the non-Ad cell culture, while the opposite phenomenon did not occur. This indicates that the source of non-Ad/ Pax7(-)/laminin(+) myogenic cells was present in the Sk-34 and Sk-DN stem cells and they were able to produce Ad/ Pax7(+)/ laminin(-) myogenic cells during myogenesis as primary myoblasts and situated hierarchically upstream of the latter cells.

PMID: 21274567 [PubMed - as supplied by publisher]

   
   
[Cell Therapy for Central Nervous System Disorders.]
January 29, 2011 at 10:09 AM
 

[Cell Therapy for Central Nervous System Disorders.]

No Shinkei Geka. 2011 Jan;39(1):5-23

Authors: Kanemura Y

PMID: 21270475 [PubMed - as supplied by publisher]

   
   
Spatial control of gene expression within a scaffold by localized inducer release.
January 29, 2011 at 10:09 AM
 

Spatial control of gene expression within a scaffold by localized inducer release.

Biomaterials. 2011 Jan 24;

Authors: Baraniak PR, Nelson DM, Leeson CE, Katakam AK, Friz JL, Cress DE, Hong Y, Guan J, Wagner WR

Gene expression can be controlled in genetically modified cells by employing an inducer/promoter system where presence of the inducer molecule regulates the timing and level of gene expression. By applying the principles of controlled release, it should be possible to control gene expression on a biomaterial surface by the presence or absence of inducer release from the underlying material matrix, thus avoiding alternative techniques that rely upon uptake of relatively labile DNA from material surfaces. To evaluate this concept, a modified ecdysone-responsive gene expression system was transfected into B16 murine cells and the ability of an inducer ligand, which was released from elastomeric poly(ester urethane) urea (PEUU), to initiate gene expression was studied. The synthetic inducer ligand was first loaded into PEUU to demonstrate extended release of the bioactive molecule at various loading densities over a one year period in vitro. Patterning films of PEUU variably-loaded with inducer resulted in spatially controlled cell expression of the gene product (green fluorescent protein, GFP). In porous scaffolds made from PEUU by salt leaching, where the central region was exclusively loaded with inducer, cells expressed GFP predominately in the loaded central regions whereas expression was minimal in outer regions where ligand was omitted. This scaffold system may ultimately provide a means to precisely control progenitor cell commitment in a spatially-defined manner in vivo for soft tissue repair and regeneration.

PMID: 21269687 [PubMed - as supplied by publisher]

   
   
Identification of adult nephron progenitors capable of kidney regeneration in zebrafish.
January 29, 2011 at 10:09 AM
 

Identification of adult nephron progenitors capable of kidney regeneration in zebrafish.

Nature. 2011 Jan 26;

Authors: Diep CQ, Ma D, Deo RC, Holm TM, Naylor RW, Arora N, Wingert RA, Bollig F, Djordjevic G, Lichman B, Zhu H, Ikenaga T, Ono F, Englert C, Cowan CA, Hukriede NA, Handin RI, Davidson AJ

Loss of kidney function underlies many renal diseases. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.

PMID: 21270795 [PubMed - as supplied by publisher]

   
   
Modeling and therapy of human liver diseases using induced pluripotent stem cells: How far have we come?
January 29, 2011 at 10:09 AM
 

Modeling and therapy of human liver diseases using induced pluripotent stem cells: How far have we come?

Hepatology. 2011 Feb;53(2):708-711

Authors: Soto-Gutierrez A, Tafaleng E, Kelly V, Roy-Chowdhury J, Fox IJ

PMID: 21274892 [PubMed - as supplied by publisher]

   
   
Interferon-α in acute myeloid leukemia: an old drug revisited.
January 29, 2011 at 10:09 AM
 

Interferon-α in acute myeloid leukemia: an old drug revisited.

Leukemia. 2011 Jan 28;

Authors: Anguille S, Lion E, Willemen Y, Van Tendeloo VF, Berneman ZN, Smits EL

Interferon-α (IFN-α), a type I IFN, is a well-known antitumoral agent. The investigation of its clinical properties in acute myeloid leukemia (AML) has been prompted by its pleiotropic antiproliferative and immune effects. So far, integration of IFN-α in the therapeutic arsenal against AML has been modest in view of the divergent results of clinical trials. Recent insights into the key pharmacokinetic determinants of the clinical efficacy of IFN along with advances in its pharmaceutical formulation, have sparked renewed interest in its use. This paper reviews the possible applicability of IFN-α in the treatment of AML and provides a rational basis to re-explore its efficacy in clinical trials.Leukemia advance online publication, 28 January 2011; doi:10.1038/leu.2010.324.

PMID: 21274002 [PubMed - as supplied by publisher]

   
   
A Peptide Mimetic of the Connexin43 Carboxyl Terminus Reduces Gap Junction Remodeling and Induced Arrhythmia Following Ventricular Injury.
January 29, 2011 at 10:09 AM
 

A Peptide Mimetic of the Connexin43 Carboxyl Terminus Reduces Gap Junction Remodeling and Induced Arrhythmia Following Ventricular Injury.

Circ Res. 2011 Jan 27;

Authors: O'Quinn MP, Palatinus JA, Harris BS, Hewett KW, Gourdie RG

Rationale: Remodeling of connexin (Cx)43 gap junctions (GJs) is linked to ventricular arrhythmia. Objectives: A peptide mimetic of the carboxyl terminal (CT) of Cx43, incorporating a postsynaptic density-95/disks-large/ZO-1 (PDZ)-binding domain, reduces Cx43/ZO-1 interaction and GJ size remodeling in vitro. Here, we determined: (1) whether the Cx43-CT mimetic αCT1 altered GJ remodeling following left ventricular (LV) injury in vivo; (2) whether αCT1 affected arrhythmic propensity; and (3) the mechanism of αCT1 effects on arrhythmogenicity and GJ remodeling. Methods and Results: A cryoinjury model generating a reproducible wound and injury border zone (IBZ) in the LV was used. Adherent methylcellulose patches formulated to locally release αCT1 (<48 hours) were placed on cryoinjuries. Relative to controls, Cx43/ZO-1 colocalization in the IBZ was reduced by αCT1 by 24 hours after injury. Programmed electric stimulation ex vivo and optical mapping of voltage transients indicated that peptide-treated hearts showed reduced inducible arrhythmias and increased ventricular depolarization rates 7 to 9 days after injury. At 24 hours and 1 week after injury, αCT1-treated hearts maintained Cx43 in intercalated disks (IDs) in the IBZ, whereas by 1 week after injury, controls demonstrated Cx43 remodeling from IDs to lateralized distributions. Over a postinjury time course of 1 week, αCT1-treated IBZs showed increased Cx43 phosphorylation at serine368 (Cx43-pS368) relative to control tissues. In biochemical assays, αCT1 promoted phosphorylation of serine368 by protein kinase (PK)C-ε in a dose-dependent manner that was modulated by, but did not require ZO-1 PDZ2. Conclusions: αCT1 increases Cx43-pS368 in vitro in a PKC-ε-dependent manner and in the IBZ in vivo acutely following ventricular injury. αCT1-mediated increase in Cx43-pS368 phosphorylation may contribute to reductions in inducible-arrhythmia following injury.

PMID: 21273554 [PubMed - as supplied by publisher]

   
   
The use of whole organ decellularization for the generation of a vascularized liver organoid.
January 29, 2011 at 10:09 AM
 

The use of whole organ decellularization for the generation of a vascularized liver organoid.

Hepatology. 2011 Feb;53(2):604-617

Authors: Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S

A major roadblock to successful organ bioengineering is the need for a functional vascular network within the engineered tissue. Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. Livers from different species were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network. The decellularized vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. The vascular network was used to reseed the scaffolds with human fetal liver and endothelial cells. These cells engrafted in their putative native locations within the decellularized organ and displayed typical endothelial, hepatic, and biliary epithelial markers, thus creating a liver-like tissue in vitro. Conclusion: These results represent a significant advancement in the bioengineering of whole organs. This technology may provide the necessary tools to produce the first fully functional bioengineered livers for organ transplantation and drug discovery. (HEPATOLOGY 2011;53:604-617).

PMID: 21274881 [PubMed - as supplied by publisher]

   
   
Chronic fetal hypoxia produces selective brain injury associated with altered nitric oxide synthases.
January 29, 2011 at 10:09 AM
 

Chronic fetal hypoxia produces selective brain injury associated with altered nitric oxide synthases.

Am J Obstet Gynecol. 2011 Jan 26;

Authors: Dong Y, Yu Z, Sun Y, Zhou H, Stites J, Newell K, Weiner CP

OBJECTIVE:: The purpose of this study was to investigate the impact of chronic hypoxia on the nitric oxide synthase isoenzymes in specific brain structures. STUDY DESIGN:: Time-mated pregnant guinea pigs were exposed to 10.5% molecular oxygen for 14 days (animals with chronic fetal hypoxia; HPX) or room air (control animals; NMX); L-N6-(1-iminoethyl)-lysine (L-NIL; an inducible nitric oxide synthase inhibitor, 1 mg/kg/d) was administered to HPX group for 14 days (L-NIL + HPX). Fetal brains were harvested at term. Multilabeled immunofluorescence was used to generate a brain injury map. Laser capture microdissection and quantitative polymerase chain reaction were applied; cell injury markers, apoptosis activation, neuron loss, total nitric oxide, and the levels of individual nitric oxide synthase isoenzymes were quantified. RESULTS:: Chronic hypoxia causes selective fetal brain injury rather than global. Injury is associated with differentially affected nitric oxide synthases in both neurons and glial cells, with inducible macrophage-type nitric oxide synthase up-regulated at all injury sites. L-NIL attenuated the injury, despite continued hypoxia. CONCLUSION:: These studies demonstrate that chronic hypoxia selectively injures the fetal brain in part by the differential regulation of nitric oxide synthase isoenzymes in an anatomic- and cell-specific manner.

PMID: 21272843 [PubMed - as supplied by publisher]

   
   
Regulation of cellular responses to macroporous inorganic films prepared by the inverse-opal method.
January 29, 2011 at 10:09 AM
 

Regulation of cellular responses to macroporous inorganic films prepared by the inverse-opal method.

Colloids Surf B Biointerfaces. 2011 Jan 7;

Authors: Orita T, Tomita M, Kato K

Regenerative medicine for repairing damaged body tissues has recently become critically important. Cell culture scaffolds are required for the control of cell attachment, proliferation, and differentiation in in vitro cell cultures. A new strategy to control cell adhesion, morphology, and proliferation was developed by culturing mouse osteoblast-like MC3T3-E1 cells on novel cell culture scaffolds fabricated using ordered nanometer-sized pores (100, 300, 500, and 1000nm). Results of this study indicate that after 72h of incubation, the number of cells cultured on a silica film with a pore size of 1000nm was similar to or slightly lower than that cultured on a non-porous control silica film. Films with 100-500nm pore sizes, however, resulted in the cell growth inhibition. Morphology of the cultured cells revealed increased elongation and the formation of actin stress fibers was virtually absent on macroporous silica films with 100-500nm pore size. Vinculin molecules expressed in cells cultured on the non-porous silica films showed many clear focal adhesions, whereas focal contacts were insufficiently formed in cells cultured on macroporous films. The influence of hydroxyapatite (HAp) and alumina scaffolds on the behavior of MC3T3-E1 cells was also evaluated. The proliferation rate of MC3T3-E1 cells cultured on HAp films with 1000nm pore size was increased to approximately 20% above than that obtained of cells cultured on non-porous HAp films. These results demonstrate that the pore size and constituents of films play a role in controlling the morphology and proliferation rate of MC3T3-E1cells.

PMID: 21273052 [PubMed - as supplied by publisher]

   
   
Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells.
January 29, 2011 at 10:09 AM
 

Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells.

Lasers Med Sci. 2011 Jan 28;

Authors: Alghamdi KM, Kumar A, Moussa NA

The aim of this work is to review the available literature on the details of low-level laser therapy (LLLT) use for the enhancement of the proliferation of various cultured cell lines including stem cells. A cell culture is one of the most useful techniques in science, particularly in the production of viral vaccines and hybrid cell lines. However, the growth rate of some of the much-needed mammalian cells is slow. LLLT can enhance the proliferation rate of various cell lines. Literature review from 1923 to 2010. By investigating the outcome of LLLT on cell cultures, many articles report that it produces higher rates of ATP, RNA, and DNA synthesis in stem cells and other cell lines. Thus, LLLT improves the proliferation of the cells without causing any cytotoxic effects. Mainly, helium neon and gallium-aluminum-arsenide (Ga-Al-As) lasers are used for LLLT on cultured cells. The results of LLLT also vary according to the applied energy density and wavelengths to which the target cells are subjected. This review suggests that an energy density value of 0.5 to 4.0 J/cm(2) and a visible spectrum ranging from 600 to 700 nm of LLLT are very helpful in enhancing the proliferation rate of various cell lines. With the appropriate use of LLLT, the proliferation rate of cultured cells, including stem cells, can be increased, which would be very useful in tissue engineering and regenerative medicine.

PMID: 21274733 [PubMed - as supplied by publisher]

   
   
Distinct physiological and behavioural functions for parental alleles of imprinted Grb10.
January 29, 2011 at 10:09 AM
 

Distinct physiological and behavioural functions for parental alleles of imprinted Grb10.

Nature. 2011 Jan 27;469(7331):534-538

Authors: Garfield AS, Cowley M, Smith FM, Moorwood K, Stewart-Cox JE, Gilroy K, Baker S, Xia J, Dalley JW, Hurst LD, Wilkinson LS, Isles AR, Ward A

Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development, but also postnatal functions including energy homeostasis and behaviour. When the two parental alleles are unequally represented within a social group (when there is sex bias in dispersal and/or variance in reproductive success), imprinted genes may evolve to modulate social behaviour, although so far no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10-deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue-specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus Grb10 is, so far, a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues.

PMID: 21270893 [PubMed - as supplied by publisher]

   
   
Regulation of Nm23-H1 and cell invasiveness by Kaposi's sarcoma-associated herpesvirus.
January 29, 2011 at 10:09 AM
 

Regulation of Nm23-H1 and cell invasiveness by Kaposi's sarcoma-associated herpesvirus.

J Virol. 2011 Jan 26;

Authors: Qin Z, Dai L, Toole B, Robertson E, Parsons C

The Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS), and the induction of an invasive cellular phenotype by KSHV following de novo infection is an important pathogenic component mediating tumor progression. The metastasis suppressor gene known as Nm23-H1 regulates tumor cell invasiveness, but whether KSHV itself regulates Nm23-H1 expression or subcellular localization, and whether this impacts cell invasiveness, has not been established. We found that KSHV increases expression and nuclear translocation of Nm23-H1, and that nuclear translocation of Nm23-H1 is regulated by the KSHV-encoded latency-associated nuclear antigen (LANA). Moreover, activation of the Ras-BRaf-MAPK signal transduction pathway, secretion of pro-migratory factors associated with this pathway, and cell invasiveness are dependent on KSHV regulation of Nm23-H1. Finally, induction of cytoplasmic overexpression of Nm23-H1 using a pharmacologic inhibitor of DNA methylation reduced KSHV-associated Ras-BRaf-MAPK pathway activation and suppressed KSHV-induced invasiveness. These data provide the first evidence for KSHV regulation of Nm23-H1 as a mechanism for KSHV induction of an invasive cellular phenotype and support the potential utility of targeting Nm23-H1 as a therapeutic approach for the treatment of KS.

PMID: 21270158 [PubMed - as supplied by publisher]

   
   
CD45 Deficiency Drives Amyloid-{beta} Peptide Oligomers and Neuronal Loss in Alzheimer's Disease Mice.
January 29, 2011 at 10:09 AM
 

CD45 Deficiency Drives Amyloid-{beta} Peptide Oligomers and Neuronal Loss in Alzheimer's Disease Mice.

J Neurosci. 2011 Jan 26;31(4):1355-1365

Authors: Zhu Y, Hou H, Rezai-Zadeh K, Giunta B, Ruscin A, Gemma C, Jin J, Dragicevic N, Bradshaw P, Rasool S, Glabe CG, Ehrhart J, Bickford P, Mori T, Obregon D, Town T, Tan J

Converging lines of evidence indicate dysregulation of the key immunoregulatory molecule CD45 (also known as leukocyte common antigen) in Alzheimer's disease (AD). We report that transgenic mice overproducing amyloid-β peptide (Aβ) but deficient in CD45 (PSAPP/CD45(-/-) mice) faithfully recapitulate AD neuropathology. Specifically, we find increased abundance of cerebral intracellular and extracellular soluble oligomeric and insoluble Aβ, decreased plasma soluble Aβ, increased abundance of microglial neurotoxic cytokines tumor necrosis factor-α and interleukin-1β, and neuronal loss in PSAPP/CD45(-/-) mice compared with CD45-sufficient PSAPP littermates (bearing mutant human amyloid precursor protein and mutant human presenilin-1 transgenes). After CD45 ablation, in vitro and in vivo studies demonstrate an anti-Aβ phagocytic but proinflammatory microglial phenotype. This form of microglial activation occurs with elevated Aβ oligomers and neural injury and loss as determined by decreased ratio of anti-apoptotic Bcl-xL to proapoptotic Bax, increased activated caspase-3, mitochondrial dysfunction, and loss of cortical neurons in PSAPP/CD45(-/-) mice. These data show that deficiency in CD45 activity leads to brain accumulation of neurotoxic Aβ oligomers and validate CD45-mediated microglial clearance of oligomeric Aβ as a novel AD therapeutic target.

PMID: 21273420 [PubMed - as supplied by publisher]

   
   
Deformability-based cell classification and enrichment using inertial microfluidics.
January 29, 2011 at 10:09 AM
 

Deformability-based cell classification and enrichment using inertial microfluidics.

Lab Chip. 2011 Jan 27;

Authors: Hur SC, Henderson-Maclennan NK, McCabe ER, Di Carlo D

The ability to detect and isolate rare target cells from heterogeneous samples is in high demand in cell biology research, immunology, tissue engineering and medicine. Techniques allowing label-free cell enrichment or detection are especially important to reduce the complexity and costs towards clinical applications. Single-cell deformability has recently been recognized as a unique label-free biomarker for cell phenotype with implications for assessment of cancer invasiveness. Using a unique combination of fluid dynamic effects in a microfluidic system, we demonstrate high-throughput continuous label-free cell classification and enrichment based on cell size and deformability. The system takes advantage of a balance between deformability-induced and inertial lift forces as cells travel in a microchannel flow. Particles and droplets with varied elasticity and viscosity were found to have separate lateral dynamic equilibrium positions due to this balance of forces. We applied this system to successfully classify various cell types using cell size and deformability as distinguishing markers. Furthermore, using differences in dynamic equilibrium positions, we adapted the system to conduct passive, label-free and continuous cell enrichment based on these markers, enabling off-chip sample collection without significant gene expression changes. The presented method has practical potential for high-throughput deformability measurements and cost-effective cell separation to obtain viable target cells of interest in cancer research, immunology, and regenerative medicine.

PMID: 21271000 [PubMed - as supplied by publisher]

   
   
Portable nanofiber meshes dictate cell orientation throughout three dimensional hydrogels.
January 29, 2011 at 10:09 AM
 

Portable nanofiber meshes dictate cell orientation throughout three dimensional hydrogels.

Nanomedicine. 2011 Jan 24;

Authors: Yang Y, Wimpenny I, Ahearne M

In this study, a new technique which controls individual cell orientation via nanofiber meshes within three dimensional (3D) hydrogels is reported. Highly aligned and fragile electrospun nanofibers (av. ϕ500 nm) are manufactured into portable and handleable meshes with average line density of 45 nanofiber/100 μm and thickness ranging between 0.5 and 3.0 μm. Through a facile and reproducible fabrication process, the nanofiber meshes can be incorporated into 3D hydrogels via a bottom-up, layer-by-layer assembly process, resulting in macroscopic and highly organized scaffolds. The nanofibers dictated the orientation of the cytoskeleton of individual cells in a very precise manner, allowing altering the orientation of a cell population throughout the thickness of the hydrogel. Addition of nanofibers affected cell phenotype and protein synthesis. This nanofiber-cell-hydrogel composite enables replication of the cellular and matrix architecture found in many natural tissues, offering a novel protocol for electrospun nanofibers in regenerative medicine and bioengineering.

PMID: 21272664 [PubMed - as supplied by publisher]

   
   
Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells.
January 29, 2011 at 8:18 AM
 

Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells.

Lasers Med Sci. 2011 Jan 28;

Authors: Alghamdi KM, Kumar A, Moussa NA

The aim of this work is to review the available literature on the details of low-level laser therapy (LLLT) use for the enhancement of the proliferation of various cultured cell lines including stem cells. A cell culture is one of the most useful techniques in science, particularly in the production of viral vaccines and hybrid cell lines. However, the growth rate of some of the much-needed mammalian cells is slow. LLLT can enhance the proliferation rate of various cell lines. Literature review from 1923 to 2010. By investigating the outcome of LLLT on cell cultures, many articles report that it produces higher rates of ATP, RNA, and DNA synthesis in stem cells and other cell lines. Thus, LLLT improves the proliferation of the cells without causing any cytotoxic effects. Mainly, helium neon and gallium-aluminum-arsenide (Ga-Al-As) lasers are used for LLLT on cultured cells. The results of LLLT also vary according to the applied energy density and wavelengths to which the target cells are subjected. This review suggests that an energy density value of 0.5 to 4.0 J/cm(2) and a visible spectrum ranging from 600 to 700 nm of LLLT are very helpful in enhancing the proliferation rate of various cell lines. With the appropriate use of LLLT, the proliferation rate of cultured cells, including stem cells, can be increased, which would be very useful in tissue engineering and regenerative medicine.

PMID: 21274733 [PubMed - as supplied by publisher]

   
   
Thermal, dynamic mechanical, and dielectric analyses of some polyurethane biocomposites.
January 29, 2011 at 8:18 AM
 

Thermal, dynamic mechanical, and dielectric analyses of some polyurethane biocomposites.

J Biomater Appl. 2011 Jan 27;

Authors: Macocinschi D, Filip D, Vlad S, Cristea M, Musteata V, Ibanescu S

Polymer biocomposites based on segmented poly(ester urethane) and extracellular matrix components have been prepared for the development of tissue engineering applications with improved biological characteristics of the materials in contact with blood and tissues for long periods. Thermal, dynamical, and dielectrical analyses were employed to study the molecular dynamics of these materials and the influence of changing the physical network morphology and hydrogen bond interactions accompanied by phase transitions, interfacial effects, and polarization or conductivity. All phenomena that concur in the tested materials are evaluated by cross-examination of the dynamic mechanical characteristic properties (storage modulus, loss modulus, and loss factor) and dielectric properties (relative permittivity, relative loss factor, and loss tangent) as a function of temperature. Comparative aspects were elucidated by calculating the apparent activation energies of multiplex experiments.

PMID: 21273260 [PubMed - as supplied by publisher]

   
   
Characterizations of Chondrocyte Attachment and Proliferation Scaffolds of PLLA and PBSA for Use in Cartilage Tissue Engineering.
January 29, 2011 at 8:18 AM
 

Characterizations of Chondrocyte Attachment and Proliferation Scaffolds of PLLA and PBSA for Use in Cartilage Tissue Engineering.

J Biomater Appl. 2011 Jan 27;

Authors: Wei JD, Tseng H, Chen ET, Hung CH, Liang YC, Sheu MT, Chen CH

The influence of physical characteristics of electrospun three-dimensional (3D) fibrous scaffolds based on polybutylene succinate-co-adipate (PBSA) and poly L-lactic acid (PLLA) on the culture of primary human chondrocytes (PHCs) in terms of cell attachment, proliferation, and re-differentiation was investigated. Physical characteristics assessed for two polymers electrospun at two different delivery rates (PBSA-3, PBSA-16, PLLA-3, and PLLA-16) including average fiber diameter, average pore diameter, porosity, and contact angle. Results demonstrated that 3D fibrous scaffolds are better for PHCs' attachment than two-dimensional (2D) casting films made of the same polymeric materials. It was also found that 3D fibrous scaffolds are appropriate architecture for the proliferation of PHCs than 2D casting films and dependent upon the polymer used. Histological analysis revealed that a significant amount of PHC was found to be growing only within layers of PLLA fibrous scaffolds. The mitochondrial ribonucleic acid (mRNA) expression of both aggrecan and type II collagen by PHCs cultured in tissue culture polystyrene for 28 days decreased significantly. The mRNA expression of both aggrecan and type II collagen by PHCs cultured in PBSA scaffolds increased from 14 to 28 days, whereas only mRNA expression of aggrecan cultured in both PLLA scaffolds increased from 14 to 28 days.

PMID: 21273264 [PubMed - as supplied by publisher]

   
   
Development of conical soluble phosphate glass fibers for directional tissue growth.
January 29, 2011 at 8:18 AM
 

Development of conical soluble phosphate glass fibers for directional tissue growth.

J Biomater Appl. 2011 Jan 27;

Authors: Alekseeva T, Neel EA, Knowles JC, Brown RA

One of the challenges of tissue engineering is the regulation of vascularization and innervations of the implant by the host. Here, we propose that using soluble phosphate glass (SPG) fibers, incorporated in dense collagen constructs will allow us to control the rate and direction of tissue ingrowth. The idea here was to generate channels with tailored direction using conical phosphate glass fibers. The changing surface area-to-mass ratio of conical fibers will make them to dissolve faster from their narrow ends opening up channels in that direction ahead of any ingrowing cells. In this study, we show that SPG fibers can be manipulated to produce conical shape fibers using graded dissolution. Our result shows that 40 µm fibers of composition ratio 0.5 (P(2)O(5)):0.25 (CaO):0.25 (Na(2)O) and dissolution time of 8-10 h have a mean reduction in fiber diameter of 8.85 ± 2.8 µm over 19.5 mm fiber length, i.e., a mean rate of 0.5 µm/mm (n = 20) change. These conically shaped fibers can also be manipulated and potentially used to promote uniaxial cell-tissue ingrowth for improved innervations and vascularization of tissue engineered constructs.

PMID: 21273258 [PubMed - as supplied by publisher]

   
   
[Stem cells and cell therapy: on the eve of scientific approach].
January 29, 2011 at 7:30 AM
 

[Stem cells and cell therapy: on the eve of scientific approach].

Tsitologiia. 2010;52(11):918-20

Authors:

Cell therapy and the stem cells (SC) have become a popular topic during last time. The theme is cluttered with numerous publications of questionable reliability. Not all methods applied in praxis are founded on evidence-based research. In the abundant literature, there is a gap between the supposed SC's healing properties associated with their capability to migrate to and engraft in injured tissue, and lack of clear morphological evidence thereof. Accordingly, there is a gap between advertizing and the better part of professional literature: the former speaks about rejuvenation of tissues, and the latter explains sometimes questionable therapeutic effects by paracrine or immunomodulating mechanisms, secretion of cytokines and growth factors. However, a SC is an undifferentiated cell, and a specific and efficient paracrine function can hardly be awaited from it as compared to others, more differentiated cells. It should be noted in conclusion that the main problem with the SC and cell therapy is commercial influence. Probably, experience of some foreign countries should be studied, where moves have been made to stop the use of unproven treatments, including some stem cell therapy.

PMID: 21268850 [PubMed - in process]

   
   
Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.
January 29, 2011 at 7:30 AM
 

Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.

Stem Cell Res Ther. 2011 Jan 27;2(1):4

Authors: Watts AE, Yeager AE, Kopyov OV, Nixon AJ

ABSTRACT: INTRODUCTION: Tendon injury is a common problem in athletes, with poor tissue regeneration and a high rate of re-injury. Stem cell therapy is an attractive treatment modality as it may induce tissue regeneration rather than tissue repair. Currently, there are no reports on the use of pluripotent cells in a large animal tendon model in vivo. We report the use of intra-lesional injection of male, fetal derived embryonic-like stem cells (fdESC) that express Oct-4, Nanog, SSEA4, Tra 1-60, Tra 1-81 and telomerase. METHODS: Tendon injury was induced using a collagenase gel-physical defect model in the mid-metacarpal region of the superficial digital flexor tendon (SDFT) of 8 female adult Thoroughbred or Thoroughbred cross horses. Tendon lesions were treated 1 week later with intra-lesional injection of male derived fdESCs in media or media alone. Therapy was blinded and randomized. Serial ultrasound examinations were performed and final analysis at 8 weeks included magnetic resonance imaging (MRI), biochemical assays (total DNA, gylcosaminoglycan, collagen), gene expression (TNC, TNMD, SCX, COL1A1, COL3A1, COMP, DCN, MMP1, MMP3, MMP13, 18S) and histology. Differences between groups were assessed with Wilcoxon's rank sum test. RESULTS: Cell survival was demonstrated via the presence of the SRY gene in fdESC treated, but not control treated, female SDFT at the end of the trial. There were no differences in tendon matrix specific gene expression or total proteoglycan, collagen or DNA of tendon lesions between groups. Tissue architecture, tendon size, tendon lesion size, and tendon linear fiber pattern were significantly improved on histologic sections and ultrasound in the fdESC treated tendons. CONCLUSIONS: Such profound structural effects lend further support to the notion that pluripotent stem cells can effect musculoskeletal regeneration, rather than repair, even without in vitro lineage specific differentiation. Further investigation into the safety of pluripotent cellular therapy as well as the mechanisms by which repair was improved seem warranted.

PMID: 21272343 [PubMed - as supplied by publisher]

   
   
Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II.
January 29, 2011 at 7:30 AM
 

Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II.

Stroke. 2011 Jan 27;

Authors: Savitz SI, Chopp M, Deans R, Carmichael ST, Phinney D, Wechsler L

Abstract Cell-based therapies represent a new therapeutic approach for stroke. In 2007, investigators from academia, industry leaders, and members of the National Institutes of Health crafted recommendations to facilitate the translational development of cellular therapies as a novel, emerging modality for stroke from animal studies to clinical trials. This meeting was called Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) and was modeled on the format of the Stroke Therapy Academic Industry Roundtable (STAIR) meetings. Since publication of the original STEPS guidelines, there has been an explosive growth in the number of cellular products and in the number of new laboratory discoveries that impact the safety and potential efficacy of cell therapies for stroke. Any successful development of a cell product will need to take into consideration several factors, including the preclinical safety and efficacy profile, cell characterization, delivery route, in vivo biodistribution, and mechanism of action. In 2010, a second meeting called STEPS 2 was held to bring together clinical and basic science researchers with industry, regulatory, and National Institutes of Health representatives. At this meeting, participants identified critical gaps in knowledge and research areas that require further studies, updated prior guidelines, and drafted new recommendations to create a framework to guide future investigations in cell-based therapies for stroke.

PMID: 21273569 [PubMed - as supplied by publisher]

   
     
 
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