Electrical stimulation induces direct reprogramming of human dermal fibroblasts into hyaline chondrogenic cells.

The repair of articular cartilage needs a sufficient number of chondrocytes to replace the defect tissue. Direct reprogramming of fibroblasts into chondrocytes can provide a sufficient number of chondrocytes because fibroblasts can be expanded efficiently. Herein, we demonstrate for the first time that electrical stimulation can drive direct reprogramming of human dermal fibroblasts (HDFs) into hyaline chondrogenic cells. Our results shows that electrical stimulation drives condensation of HDFs and then enhances expression levels of chondrogenic markers, such as type II collagen, aggrecan, and Sox9, and decreases type I collagen levels without the addition of exogenous growth factors or gene transduction. Electrical stimulation-directly reprogrammed chondrogenic cells showed the normal karyotype. It was also found that electrical stimulation increased the secretion levels of TGF-beta1, PDGF-AA, and IGFBP-2, 3. These findings may contribute to not only novel approach of direct reprogramming but also cell therapy for cartilage regeneration.

Microstructure, Electrical and Thermal Conductivity of the As-Extruded Al-xMM (Mischmetal) Based Alloys.

The effect of addition of Mischmetal (MM) on the microstructure, electrical and thermal conductivity, and mechanical properties of the as-extruded Al-MM based alloys were investigated. The studied AlxMM alloys (where x = 0.2, 0.5, 1.0, 1.5, 2.0 and 5.0 wt.%) were cast and homogenized at 550 °C for 4 h. The cast billets were extruded into 12 mm bars with an extrusion ratio of 39 at 550 °C. The addition of MM resulted in the formation of Al11(Ce, La)3 intermetallic compounds and the area fraction of these intermetallic compounds increased with an increase in the MM content. The Al11(Ce, La)3 phase, which was distributed in the as-cast alloys, was crushed into fine particles and arrayed along the extruded direction during the extrusion process. In particular, these intermetallic compounds in the extruded Al-5.0MM alloy were distributed with a wide-band structure due to the fragmentation of the eutectic phase with a lamellar structure. As the MM content increased from 1.0 wt.% to 5.0 wt.%, the average grain size decreased remarkably from 740 to 73 µm. This was due to formation of Al11(Ce, La)3 particles during the hot extrusion process, which promoted dynamic recrystallization and suppression of grain growth. The electrical and thermal conductivity of the extruded alloys containing up to 2.0 wt.% MM were around 60.5% IACS and 230 W/m · K, respectively. However, the electrical and thermal conductivity of the extruded alloy with 5.0 wt.% MM decreased to 55.4% IACS and 206 W/m · K, respectively. As the MM content increased from 1.0 wt.% to 5.0 wt.%, the ultimate tensile strength (UTS) was improved remarkably from 74 to 119 MPa which was attributed to the grain refinement and formation of Al11(Ce, La)3 intermetallic compounds by the addition of MM.

Renal interstitial cell tumor in a dog: clinicopathologic, imaging, and histologic features.

Renal interstitial cell tumors are benign tumors of renomedullary origin; however, malignant features have not been reported in dogs, to our knowledge. A 17-y-old spayed female Maltese dog was presented to a local animal hospital with a mass in the right abdomen. Clinicopathologic findings prior to surgery revealed renal insufficiency and anemia. Imaging revealed that the right kidney was enlarged by an amorphous mass with opaque areas, indicative of mineralization. Upon histologic examination, the mass was comprised of malignant mesenchymal cells that produced mucinous matrix. The tumor cells were positive for vimentin and COX-2, but negative for pancytokeratin; the matrix stained positively with alcian blue. Therefore, the mass was diagnosed as a renal interstitial cell tumor, with malignant features. COX-2 may be useful in the diagnosis of canine renal interstitial cell tumors, similar to its diagnostic role in humans.

Effects of Mg Addition on Microstructure, Mechanical Properties, and Thermal Conductivity of As-Extruded Al-RE Alloys.

In this study, we investigated the effect of Mg addition (0, 0.5, and 1.0 wt%) on the microstructure, mechanical properties, and thermal conductivity of as-extruded Al-RE alloys. With an increase in the Mg content from 0 to 1.0 wt%, the average grain size of the alloys decreased remarkably from 740 to 130 µm and the high-angle grain boundary fraction increased from 35 to 54%. The addition of Mg resulted in the grain refinement of the Al-1.0RE alloy because of the dynamic recrystallization caused by the solute Mg atoms during the extrusion. With an increase in the Mg content from 0.5 to 1.0 wt%, thermal conductivity of the alloy decreased from 231 to 193 W/mK because of the electric scattering caused by the solute Mg atoms. With an increase in the Mg content from 0 to 1.0 wt%, the ultimate tensile strength of the alloy increased remarkably from 74 to 120 MPa, while the strain reduced from 44 to 34%. This improvement in the strength resulted from the grain refinement and solid solution strengthening due to the solute Mg atoms. The Mg addition amount affected the thermal conductivity and strength of the alloys significantly.

Electrical stimulation drives chondrogenesis of mesenchymal stem cells in the absence of exogenous growth factors.

Electrical stimulation (ES) is known to guide the development and regeneration of many tissues. However, although preclinical and clinical studies have demonstrated superior effects of ES on cartilage repair, the effects of ES on chondrogenesis remain elusive. Since mesenchyme stem cells (MSCs) have high therapeutic potential for cartilage regeneration, we investigated the actions of ES during chondrogenesis of MSCs. Herein, we demonstrate for the first time that ES enhances expression levels of chondrogenic markers, such as type II collagen, aggrecan, and Sox9, and decreases type I collagen levels, thereby inducing differentiation of MSCs into hyaline chondrogenic cells without the addition of exogenous growth factors. ES also induced MSC condensation and subsequent chondrogenesis by driving Ca2+/ATP oscillations, which are known to be essential for prechondrogenic condensation. In subsequent experiments, the effects of ES on ATP oscillations and chondrogenesis were dependent on extracellular ATP signaling via P2X4 receptors, and ES induced significant increases in TGF-ß1 and BMP2 expression. However, the inhibition of TGF-ß signaling blocked ES-driven condensation, whereas the inhibition of BMP signaling did not, indicating that TGF-ß signaling but not BMP signaling mediates ES-driven condensation. These findings may contribute to the development of electrotherapeutic strategies for cartilage repair using MSCs.