Current Concepts of Stem Cell Therapy for Chronic Spinal Cord Injury

Chronic spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have been continuously investigated in clinical trials. In addition, several more are coming down the translational pipeline. Among ongoing and completed trials are those reporting the use of mesenchymal stem cells, neural stem/progenitor cells, induced pluripotent stem cells, olfactory ensheathing cells, and Schwann cells. The advancements in stem cell technology, combined with the powerful neuroimaging modalities, can now accelerate the pathway of promising novel therapeutic strategies from bench to bedside. Various combinations of different molecular therapies have been combined with supportive scaffolds to facilitate favorable cell–material interactions. In this review, we summarized some of the most recent insights into the preclinical and clinical studies using stem cells and other supportive drugs to unlock the microenvironment in chronic SCI to treat patients with this condition. Successful future therapies will require these stem cells and other synergistic approaches to address the persistent barriers to regeneration, including glial scarring, loss of structural framework, and immunorejection.     

Analysis of alcohol oxidase isozymes in gene-disrupted strains of methylotrophic yeast Pichia methanolica

A cell-free extract of methanol-grown Pichia methanolica cells was found to contain nine alcohol oxidase (AOD) isozymes by active staining of a native polyacrylamide electrophoresis gel. Our previous study revealed that AOD in P. methanolica was encoded by two genes, MOD1 and MOD2, and the results of an experiment involving Candida boidinii as an expression host suggested that the AOD isozymes observed in P. methanolica were due to random association of Mod1p and Mod2p into an active octamer [Nakagawa et al., Yeast, 15, 1223-1230 (1999)]. This study was conducted using P. methanolica MOD1- and/or MOD2-gene disrupted strains to confirm a previous hypothesis. While the cell-free extract of the wild-type strain gave nine ladder bands, the mod1delta and mod2delta strains gave a single active AOD band corresponding to the mobilities of Mod2p and Mod1p on a native electrophoresis gel, respectively. The cell-free extract of glyceorl-grown wild-type cells gave a single band corresponding to Mod1p, showing that only MOD1 is expressed in glycerol-grown cells. While the expression of both MOD1 and MOD2 was induced by methanol, this finding and our previous observations indicated that the expression of MOD1 and MOD2 was controlled by a distinct regulatory mechanism in P. methanolica.     

Synthesis and crystal structure analysis of complex hydride Mg(BH4)(NH2)

Complex hydride Mg(BH₄)(NH₂), which consists of double anion BH₄⁻ and NH₂⁻, was synthesized and the crystal structure was analyzed by synchrotron X-ray diffraction. The mixture sample of Mg(BH₄)₂ + Mg(NH₂)₂ prepared by ball milling was reacted and crystallized to Mg(BH₄)(NH₂) by heating at about 453 K. This crystal phase transforms into amorphous phase above 473 K and subsequently the dehydrogenation begins. The crystal structure of Mg(BH₄)(NH₂) was determined from measurement data at 453 K (chemical formula: Mg_0.94(BH₄)₁(NH₂)_0.88, crystal system: tetragonal, space group: I4₁ (No.80), Z = 8, lattice constants: a = 5.814(1), c = 20.450(4) Å at 453 K). Mg(BH₄)(NH₂) is ionic crystal which the cation (Mg²⁺) and the anions (BH₄⁻ and NH₂⁻) are stacking alternately along the c-axis direction. Two BH₄⁻ and two NH₂⁻ tetrahedrally coordinate around Mg²⁺ ion.     

Open dumping site in Asian developing countries: a potential source of polychlorinated dibenz-p-dioxins and polychlorinated dibenzofurans

Open landfill dumping areas for municipal wastes in Asian developing countries have recently received particular attention with regard to environmental pollution problems. Because of the uncontrolled burning of solid wastes, elevated contamination by various toxic chemicals including dioxins and related compounds in these dumping sites has been anticipated. In this study, concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) were determined in soils from dumping sites in the Philippines, Cambodia, India, and Vietnam. Residue concentrations of PCDD/Fs and coplanar PCBs in dumping site soils were apparently greater than those in soils collected in agricultural or urban areas far from dumping sites, suggesting that dumping sites are potential sources of PCDD/Fs and related compounds. Observed PCDD/F concentrations in soils from dumping sites in the Philippines and Cambodia were comparable or higher than those reported for dioxin-contaminated locations in the world (e.g., near the municipal waste incinerators and open landfill dumping sites). Homologue profiles of PCDD/Fs in dumping site soils from the Philippines and, to a lesser extent, from Cambodia and India reflected patterns of samples representing typical emissions, while profiles of agricultural or urban soils were similar to those of typical environmental sinks. This result suggests recent formation of PCDD/Fs in dumping site areas and that open dumping sites are a potential source of dioxins in Asian developing countries. Uncontrolled combustions of solid wastes by waste pickers, generation of methane gas, and low-temperature burning can be major factors for the formation of dioxins in dumping sites. Elevated fluxes of PCDD/Fs to soils in dumping sites were encountered in the Philippines, Cambodia, India, and Vietnam-Hanoi, and these levels were higher than those reported for other countries. Considerable loading rates of PCDD/Fs in the dumping sites of these countries were observed, ranging from 20 to 3900 mg/yr (0.12-35 mg TEQ/yr). PCDD/F concentrations in some soil samples from the Philippines, Cambodia, India, and Vietnam-Hanoi exceeded environmental guideline values, suggesting potential health effects on humans and wildlife living near these dumping sites. The estimated intakes of dioxins via soil ingestion and dermal exposure for children were higher than those for adults, suggesting greater risk of dioxin exposure for children in dumping sites. To our knowledge, this is the first comprehensive study on PCDD/Fs contamination in open dumping sites of Asian developing countries. On the basis of the result of this study, we have addressed a new environmental issue that open dumping sites are potential sources of PCDD/Fs and related compounds, and dioxin contamination in dumping sites may become a key environmental problem in developing countries.     

Lipid peroxidation-derived cytotoxic aldehyde, 4-hydroxy-2-nonenal in smoked pork

The contents of 4-Hydroxy-2-nonenal (HNE), cytotoxic aldehyde, in smoked meat products (ham, bacon and sausage) were analyzed. All the samples analyzed contained HNE, although large differences in the contents between the different samples were observed. In one lot of ham (H1) and wiener sausage (WS1) a high level in HNE was observed. The changes of HNE contents of pork meats containing 0, 0.1, 0.5 and 1% Sugi wood vinegar (SWV) stored at 0?°C were also analyzed for 7 days. As an index of lipid peroxidation level, malonaldehyde (MA) contents were also analyzed in these samples. After 7 days of storage, HNE was detected only in pork meats containing 1% SWV and the level was similar to those of H1 and WS1. Judging from MA contents, SWV may act as a pro-oxidant in pork meats and HNE may accumulate in pork in which lipid peroxidation is in progress.     

Micropatterned organoid culture of rat hepatocytes and HepG2 cells

The culture of liver cell organoids (multicellular aggregates) such as spheroids or cylindroids, which can strongly express liver functions, has been advocated as a useful technique that has advantages over monolayer culture. This paper describes a micropatterning technique for obtaining spheroids and cylindroids by using rat hepatocytes or HepG2 cells. We developed culture chips that comprised multiple, circular or rectangular microwells; the bottom surface of each microwell was modified with collagen to create a cell adhesion area, and the entire microwell, excluding the collagen-coated spots, was modified with polyethylene glycol (PEG) to create a nonadhesive area. Rat hepatocytes and HepG2 cells formed uniform spheroids and cylindroids on the circular and rectangular chips, respectively. Consequently, two-dimensional micropatterned chips containing homogeneous spheroids or cylindroids were generated. The expression of liver functions (protein secretion and ammonia removal) was greater in the spheroids and cylindroids than in the monolayer culture, and this expression was maintained for at least 2 weeks of culture. Thus, this chip technology has potential for use in various applications that involve organoid culture.     

Combined non-gray radiative and conductive heat transfer in solar collector glass cover

A rigorous approach for the radiative heat transfer analysis in solar collector glazing is developed. The model allows a more accurate prediction of thermal performance of a solar collector system. The glass material is analysed as a non-gray plane-parallel medium subjected to solar and thermal irradiations in the one-dimensional case using the Radiation Element Method by Ray Emission Model (REM by REM).This method is used to analyse the combined non-gray convective, conductive and radiative heat transfer in glass medium. The boundary surfaces of the glass are specular. The spectral dependence of the relevant radiation properties of glass (i.e. specular reflectivity, refraction angle and absorption coefficient) are taken into consideration. Both collimated and diffuse incident irradiation are applied at the boundary surfaces using the spectral solar model proposed by Bird and Riordan. The optical constants of a commercial ordinary clear glass material have been used. These optical constants (100 values) of real and imaginary parts of the complex refractive index of the glass material cover the range of interest for calculating the solar and thermal radiative heat transfer through the solar collector glass cover. The model allows the calculation of the steady-state heat flux and temperature distribution within the glass layer. The effect of both conduction and radiation in the heat transfer process is examined. It has been shown that the real and imaginary parts of the complex refractive index have a substantial effect on the layer temperature distribution. The computational time for predicting the combined heat transfer in such a system is very long for the non-gray case with 100 values of n and k. Therefore, a simplified non-gray model with 10 values of n and k and two semi-gray models have been proposed for rapid computations. A comparison of the proposed models with the reference non-gray case is presented. The result shows that 10 bandwidths could be used for rapid computation with a very high level of accuracy.     

Cover Picture: Assembly and Photoinduced Organization of Mono‐ and Oligopeptide Molecules Containing an Azobenzene Moiety (Adv. Funct. Mater. 9/2007)

An illustration of the phototriggered organization and dispersion of tri‐peptide‐substituted azobenzene derivatives, as reported on p. 1507 by Yoko Matsuzawa and co‐workers. The tri‐peptide units form a beta‐sheet structure through hydrogen bonding to assemble a fibrous network system. Cis–trans photoisomerization of the azobenzene moiety leads to a large polarity change of the component molecule to break and re‐form hydrogen bonds between the tri‐peptide units. Assembled systems consisting of an azobenzene moiety as the photofunctional component and valyl units as the network backbone are investigated. The molecular ordering of these assemblies is examined by spectroscopy and theoretical calculations. The number of valyl units greatly influences the molecular order in the organized systems. Only N‐(L ‐valyl‐L ‐valyl‐L ‐valyl)azobenzene‐4‐carboxamide ( 3 ) forms a complete β‐sheet structure in this artificial assembly. Upon photoirradiation, the azobenzene moieties isomerize completely, revealing the reversibility in the structural organization through the flexibility of the β‐sheet network in this system.     

Ultrafine grain formation in face centered cubic metals during severe plastic deformation

The evolution mechanisms of new high-angle boundaries as well as ultrafine grains at large strains were studied by means of multidirectional forging (MDF) of pure copper at low temperature and aluminum alloy at high temperature, where dynamic recovery operates as a main restoration process. The structural changes can be characterized by the evolution of deformation bands such as microshear or kink bands at moderate strains. Multidirectional forging accelerates the evolution of many mutually crossing microshear or kink bands developed in various directions. The misorientations between (sub)grains increased gradually with increasing cumulative strain, finally leading to the development of a new fine-grained structure. The dynamic grain formation can be resulted from in situ or continuous dynamic recrystallization which is discussed in detail.