Enhancement of arsenic trioxide-mediated changes in human induced pluripotent stem cells (IPS).

Induced pluripotent stem cells (IPS) are an artificially derived type of pluripotent stem cell, showing many of the same characteristics as natural pluripotent stem cells. IPS are a hopeful therapeutic model; however there is a critical need to determine their response to environmental toxins. Effects of arsenic on cells have been studied extensively; however, its effect on IPS is yet to be elucidated. Arsenic trioxide (ATO) has been shown to inhibit cell proliferation, induce apoptosis and genotoxicity in many cells. Based on ATOs action in other cells, we hypothesize that it will induce alterations in morphology, inhibit cell viability and induce a genotoxic effect on IPS. Cells were treated for 24 hours with ATO (0-9 µg/mL). Cell morphology, viability and DNA damage were documented. Results indicated sufficient changes in morphology of cell colonies mainly in cell ability to maintain grouping and ability to remain adherent. Cell viability decreased in a dose dependent manner. There were significant increases in tail length and moment as well as destruction of intact DNA as concentration increased. Exposure to ATO resulted in a reproducible dose dependent sequence of events marked by changes in morphology, decrease of cell viability, and induction of genotoxicity in IPS.

Effects of sustained delivery of IGF-1 in a rat degenerative disc model.

Degenerative disc disease is a leading source of pain as well as increased health care costs in the United States, and research efforts into understanding the pathophysiology of this disease are necessary for the development of new management strategies. Addition of growth factors to stimulate chondrocyte development are on the horizon as new treatment modalities for degenerative disc disease, but increasing growth factor concentrations in the body may have adverse affects on vital organs. The objective of this study was to investigate the use of sustained delivery of insulin-like growth factor-1 (IGF-1) for treatment of degenerative discs using the adult male rat as a model. The results showed increased chondrocyte proliferation and decreased apoptosis at the traumatized disc after 28 days. Analysis of the vital organs revealed slight increases in kidney wet weights, and closer histomorphometric evaluation of the tissue revealed changes in the proximal tubules. Further investigation to evaluate the potential physiological or pathophysioloigcal effects of the growth factors at the organ levels is warranted before use as therapeutic agent to treat degenerative disc disease.