Human embryonic stem (hES) cells have been proposed as a source of various cell types for cell replacement therapy. Besides their potential in therapeutic uses, ES cells also have other potential applications, such as in drug discovery and in vitro screening assays of various toxicants. Nonylphenol (NP) and octylphenol (OP) are common environmental contaminants, known to disrupt the reproductive and endocrine system. However, little is known about their toxicological effects on early embryonic development in humans. In this study, we used undifferentiated hES cells and the neural progenitor cells derived from them to investigate the potential toxicity of NP and OP. Our results show that the cytotoxic effects of NP and OP involve DNA fragmentation, the major characteristic of apoptosis. The NP- and OP-induced apoptosis was concomitant with the increased activity of Caspase-8 and -3. Moreover, both Fas and Fas ligand (FasL) protein expressions were markedly increased in the NP- or OP-exposed hES cells. These results suggest that NP and OP are able to trigger apoptosis in hES cells via a pathway dependent on caspase activation and Fas-FasL interaction. In particular, hES cell-derived neural progenitor cells had a higher sensitivity to the toxicants than undifferentiated hES cells, thereby suggesting that the toxic stress response may differ depending on the developmental stage. These findings offer new perspectives for understanding the fundamental mechanisms in chemical-induced apoptosis in hES cells.

Vascular endothelial growth factor (VEGF), a potent mitogen for vascular endothelial cells, has been suggested as a modulator that is involved in neurogenesis as well as angiogenesis. Here, we directly examined the effect of VEGF on neuroectodermal differentiation using human embryonic stem cells (hESCs). VEGF treatment upregulated the expression of neuroectodermal genes (Sox1 and Nestin) during germ layer formation in embryoid bodies (EBs) and efficiently increased the number of neural rosettes expressing both Pax6 and Nestin. The neural progenitors generated from VEGF-treated EBs further differentiated into cells that showed a similar pattern of gene expression observed in the development of dopaminergic neurons upon terminal differentiation. These results support the neurogenic effect of VEGF on hESC differentiation.

PurposeTo analyze the contact mechanics of the femoral component and polyethylene of the Low Contact Stress rotating platform (LCS-RP) in nonweight bearing and weight bearing conditions using full flexion lateral radiographs.Materials and MethodsFrom May 2009 to December 2013, 58 knees in 41 patients diagnosed with osteoarthritis and treated with total knee arthroplasty (TKA) were included in this study. TKA was performed using an LCS-RP knee prosthesis. Full flexion lateral radiographs in both weight bearing and nonweight bearing condition were taken at least one month postoperatively (average, 28.8 months). Translation of femoral component was determined by the contact point between the femoral component and polyethylene. Maximum flexion was measured as the angle between the lines drawn at the midpoint of the femur and tibia.ResultsPosterior shift of the contact point in LCS-RP TKA was observed under weight bearing condition, which resulted in deeper flexion compared to LCS-RP TKA under nonweight bearing condition.ConclusionsIn the LCS-RP TKA, the contact point between the femoral component and polyethylene moved posteriorly under weight bearing condition, and the joint was more congruent and maximum flexion increased with weight bearing.