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Open Access Publications from the University of California

Novel Image-Based Analysis of Bone Teratogenesis Using Human Embryonic Stem Cell Model

  • Author(s): Martinez, Ivann Kenneth Carvajal
  • Advisor(s): zur Nieden, Nicole I
  • et al.

Development is an important process in the biology of an organism. This process is tightly regulated allowing this process to be responsive to signals and resistant to toxicants to prevent the occurrence of congenital diseases from occurring. Chemicals that can alter development are called teratogens and it is of great importance to identify and characterize these teratogens, especially those that are prevalently found in the environment, such as tobacco smoke. We have developed a novel method to determine teratogenic effects on bone development of toxicants, such as tobacco smoke. This method utilizes image analysis technology to automatically segment areas of calcification from phase contrast images or time-lapse videos. This allows us to quantify the amount of calcium that is being deposited by newly emerged osteoblasts cells. These osteoblasts cells were derived from human embryonic stem cells, which allows for direct comparison of effects in human subjects. Mainstream and sidestream smoke derived from commercially available conventional and "harm-reduction" tobacco product were compared to determine their teratogenic effects on osteogenesis. Mainstream smoke from all brands tested showed no observable changes in osteogenesis. However, sidestream smoke was shown to be more potent in disrupting osteogenesis by either lowering levels of calcification through a teratogenic effect or cytotoxic through cell death. "harm-reduction" product did not show any difference in effect on bone differentiation compared to conventional product, suggesting that these products offer no reduction in harm towards their effects on bone health. This study has yielded a novel method to establish teratogenicity of toxicants towards bone differentiation using data obtained from images. This method is more cost-effective, requires less sample and is environmentally safer compared to conventional method of establishing teratogenic effects of toxicants.

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