Cell-based articular cartilage repair: the link between development and regeneration.

Clinical efforts to repair damaged articular cartilage (AC) currently face major obstacles due to limited intrinsic repair capacity of the tissue and unsuccessful biological interventions. This highlights a need for better therapeutic strategies. This review summarizes the recent advances in the field of cell-based AC repair. In both animals and humans, AC defects that penetrate into the subchondral bone marrow are mainly filled with fibrocartilaginous tissue through the differentiation of bone marrow mesenchymal stem cells (MSCs), followed by degeneration of repaired cartilage and osteoarthritis (OA). Cell therapy and tissue engineering techniques using culture-expanded chondrocytes, bone marrow MSCs, or pluripotent stem cells with chondroinductive growth factors may generate cartilaginous tissue in AC defects but do not form hyaline cartilage-based articular surface because repair cells often lose chondrogenic activity or result in chondrocyte hypertrophy. The new evidence that AC and synovium develop from the same pool of precursors with similar gene profiles and that synovium-derived chondrocytes have stable chondrogenic activity has promoted use of synovium as a new cell source for AC repair. The recent finding that NFAT1 and NFAT2 transcription factors (TFs) inhibit chondrocyte hypertrophy and maintain metabolic balance in AC is a significant advance in the field of AC repair. The use of synovial MSCs and discovery of upstream transcriptional regulators that help maintain the AC phenotype have opened new avenues to improve the outcome of AC regeneration.

Association of selenium and copper with lipids in umbilical cord blood.

Altered levels of selenium and copper have been linked with altered cardiovascular disease risk factors including changes in blood triglyceride and cholesterol levels. However, it is unclear whether this can be observed prenatally. This cross-sectional study includes 274 singleton births from 2004 to 2005 in Baltimore, Maryland. We measured umbilical cord serum selenium and copper using inductively coupled plasma mass spectrometry. We evaluated exposure levels vis-à-vis umbilical cord serum triglyceride and total cholesterol concentrations in multivariable regression models adjusted for gestational age, birth weight, maternal age, race, parity, smoking, prepregnancy body mass index, n-3 fatty acids and methyl mercury. The percent difference in triglycerides comparing those in the highest v. lowest quartile of selenium was 22.3% (95% confidence interval (CI): 7.1, 39.7). For copper this was 43.8% (95% CI: 25.9, 64.3). In multivariable models including both copper and selenium as covariates, copper, but not selenium, maintained a statistically significant association with increased triglycerides (percent difference: 40.7%, 95% CI: 22.1, 62.1). There was limited evidence of a relationship of increasing selenium with increasing total cholesterol. Our findings provide evidence that higher serum copper levels are associated with higher serum triglycerides in newborns, but should be confirmed in larger studies.

An epidemic of corneal destruction caused by plasma gas sterilization. The Toxic Cell Destruction Syndrome Investigative Team.

BACKGROUND: Toxic endothelial cell destruction (TECD) syndrome after intraocular ophthalmic surgery is rare and can result from exposure to a variety of toxins. During January 8 to 14, 1998, 6 patients developed TECD with corneal edema associated with unreactive or dilated pupils at Hospital A. METHODS: A case patient was any Hospital A patient with TECD within 24 hours after surgery during January 5 to 14, 1998 (epidemic period). A control was any hospital A ophthalmic surgery patient without TECD during the epidemic period. The medical records of hospital A ophthalmology surgery patients during the pre-epidemic (ie, September 1, 1997-January 4, 1998) and epidemic periods were reviewed. Inductively coupled plasma atomic emission spectrometry was used to detect trace inorganic elements on sterilized surgical instruments. Cannulated surgical instruments and laboratory rinsates were perfused directly to the corneal endothelium of isolated rabbit and human corneas. Corneal endothelial ultrastructure and swelling were assessed. RESULTS: The rate of TECD at hospital A was higher during the epidemic than pre-epidemic period (6/12 vs 0/118, P<.001). The only change during the periods was the introduction, on November 5, 1997, of a new sterilization method, AbTox Plazlyte, for sterilization of ophthalmic surgery instruments. Findings from spectrometry revealed that copper and zinc residues were higher in instruments sterilized with Plazlyte than in those sterilized with ethylene oxide (median copper value, 7.64 mg/L vs 0.14 mg/L, respectively, P =.02; median zinc value, 5.90 mg/L vs 1.35 mg/L, respectively, P =.2). Corneal endothelial perfusion of Plazlyte sterilized-instrument rinsates or laboratory solution with copper and zinc produced irreversible damage, similar to toxic corneal endothelial destruction, to rabbit and human corneas. CONCLUSION: A new sterilization method degraded brass to copper and zinc on cannulated surgical instruments resulting in TECD of the cornea. Arch Ophthalmol. 2000;118:1167-1176

Trace metals in urine of United States residents: reference range concentrations.

We measured 13 metals in the urine of 496 United States residents to establish reference range concentrations using inductively coupled argon plasma mass spectrometry and Zeeman graphite furnace atomic absorption spectrometry. We frequently found 8 of these analytes at detectable concentrations in urine specimens: molybdenum (in 99.8%); lead (98.8%); tin (89%); thallium (77%); antimony (73.5%); manganese (73%); cesium (71%); tungsten (70%); and platinum (69.7%). The 95th percentile concentration for molybdenum was 168 micrograms/L; concentrations ranged up to 688 micrograms/L. Lead concentrations ranged up to 67 micrograms/L, and the 95th upper percentile was 6.4 micrograms/L. Tin had 95th upper percentile of 20.1 micrograms/L. Other analytes measured at detectable concentrations included barium (in 67% of the specimens); beryllium (67%); chromium (54%); thorium (44%); and cobalt (43%). In almost every case, the 95th upper percentiles of these analytes were less than 15 micrograms/L.

Regulation of creatine phosphokinase expression during differentiation of BC3H1 cells.

The intracellular mechanisms involved in the regulation of creatine phosphokinase expression in the BC3H1 muscle-like cell line have been examined under conditions of enzyme induction and repression. In the presence of low serum concentrations, BC3H1 cells cease to grow and synthesize high levels of creatine phosphokinase. When differentiated BC3H1 cultures are exposed to media containing high serum concentrations, cell division is reinitiated and further induction of creatine phosphokinase is inhibited. Accumulation of creatine phosphokinase-mRNA appears to be intimately coupled to the state of growth of BC3H1 cells. Log phase cells do not contain detectable levels of translatable creatine phosphokinase-mRNA; however, following cessation of growth, creatine phosphokinase-mRNA accumulates in approximate proportion to the increase in creatine phosphokinase activity. Reinitiation of cell division in quiescent differentiated cultures results in the arrest of further accumulation of creatine phosphokinase-mRNA but does not inhibit the translation of pre-existing creatine phosphokinase-mRNA. Under conditions of enzyme repression, however, the newly synthesized creatine phosphokinase appears to be enzymatically inactive. These results indicate that the expression of the muscle phenotype in BC3H1 cells is regulated by components present in serum and that myogenic differentiation is at least partially reversible following re-entry of quiescent cells into the cell cycle.

Multiple controls for the synthesis of muscle-specific proteins in BC3H1 cells.

The regulation of the synthesis of muscle-specific proteins has been examined in BC3H1 cells, a smooth muscle-like cell line isolated by Schubert et al. (J. Cell Biol., 1974, 61: 398-413.). The synthesis of both creatine kinase and the acetylcholine receptor appear to be under dual control, a positive control due to cell-cell contact which increases the rate of synthesis of this protein, and a negative signal, elicited by serum components, that decreases the rate of synthesis of these proteins. Induction of muscle-specific proteins in BC3H1 cells is a reversible process and can be arrested after partial induction has taken place by the addition of serum or high-molecular-weight protein fraction from serum to these cells. The high-molecular-weight protein fraction from serum is not by itself mitogenic for Bc3H1 cells and cannot be replaced by a variety of known hormones (mitogenic factors).