BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells.

Bone regeneration achieved using mesenchymal stem cells (MSCs) and nonviral gene therapy holds great promise for patients with fractures seemingly unable to heal. Previously, MSCs overexpressing bone morphogenetic proteins (BMPs) were shown to differentiate into the osteogenic lineage and induce bone formation. In the present study, we evaluated the potential of osteogenic differentiation in porcine adipose tissue- and bone marrow-derived MSCs (ASCs and BMSCs, respectively) in vitro and in vivo when induced by nucleofection with rhBMP-2 or rhBMP-6. Our assessment of the in vivo efficiency of this procedure was made using quantitative micro-computed tomography (micro-CT). Nucleofection efficiency and cell viability were similar in both cell types; however, the micro-CT analyses demonstrated that in both ASCs and BMSCs, nucleofection with rhBMP-6 generated bone tissue faster and of higher volumes than nucleofection with rhBMP-2. RhBMP-6 induced more efficient osteogenic differentiation in vitro in BMSCs, and in fact, greater osteogenic potential was identified in BMSCs both in vitro and in vivo than in ASCs. On the basis of our findings, we conclude that BMSCs nucleofected with rhBMP-6 are superior at inducing bone formation in vivo than all other groups studied.

Effects of intervertebral disk degeneration on the flexibility of the human thoracolumbar spine.

The objective of this study was to investigate the effects of intervertebral disk degeneration on the flexibility of the thoracolumbar spine in flexion and extension, both experimentally and computationally. A seven-level biomechanically tested human cadaveric spine (T11-L5) and a 3D finite element model of the same thoracolumbar spine were used for this purpose. The anatomically accurate computer model was generated from detailed computed tomography images and included the vertebral shell, the trabecular centrum, cartilage endplates, intervertebral disks, seven spinal ligament groups, and the facet joints. The cadaveric spinal segment and the specimen-specific finite element model were subjected to various compressive loads ranging from 75 to 975 N using the follower load principle and an oscillating bending moment of +/-5 Nm applied in the sagittal plane. The biomechanical behavior of the finite element model of the spine was validated with the experimental mechanical test data for the corresponding physical thoracolumbar spine specimen. In addition, the effect of intervertebral disk material property variation within the thoracolumbar spinal column on the spinal flexibility was extensively studied. The results of this study provided significant insight into how mechanical properties of the intervertebral disk influence spinal flexibility along the thoracolumbar spinal column. It was found that in order to get comparable results between experimental and computed data, the material properties of the intervertebral disks had to vary along the spinal column. However, these effects are diminished with increasing axial compressive load. Because of the trend between disk properties and spinal level, we further concluded that there might be a mechanism at play that links endplate size, body weight fraction, and segmental flexibility. More studies are needed to further investigate that relationship.

Disruption of cochlear potentials by chemical asphyxiants. Cyanide and carbon monoxide.

While ischemia, hypoxic hypoxia, and carbon monoxide (CO) have received extensive study designed to characterize mechanisms by which they disrupt cochlear function, little data are available concerning cyanide's potential to disrupt auditory function. In this study, disruption of the compound action potential (CAP) and endocochlear potential (EP) by cyanide and CO was compared in rats treated with potassium cyanide (KCN) (7 mg/kg ip), saline, CO (35 ml/kg ip), and air. Acute KCN administration significantly suppressed CAP and EP transiently. The effect was seen initially on EP with CAP impairment occurring a few minutes later. Acute CO injection also suppressed the CAP significantly, but the effect was far smaller, occurred later in time, and lasted longer than the effect of KCN. The effect of CO on EP was equivocal. There was a good correspondence between blood cyanide levels and impairment of cochlear function; carboxyhemoglobin (HbCO) levels were elevated during the period when cochlear function was impaired, but recovery of cochlear function preceded the return of normal oxyhemoglobin. Both KCN and CO had somewhat preferential effects on high-frequency tones. Repeated cyanide administration caused a persistent CAP threshold elevation despite the rapid recovery of EP and CAP observed following acute KCN administration. The data suggest that acute KCN administration has a prominent disruptive effect at the stria vascularis presumably by disrupting the electron transport chain in this metabolically active structure. The principal target for acute CO ototoxicity in the cochlea is probably not the stria vascularis.