Human stem cells, chromatin, and tissue engineering: boosting relevancy in developmental toxicity testing.
Risk assessment derives its confidence from toxicology research that is based on relevancy to human health. This article focuses on two highly topical areas of current scientific research, stem cells and chromatin biology, which present new avenues for preclinical and clinical applications, and the frontier role of tissue engineering and regeneration. Appreciating the utility and necessity of chromatin and human somatic stem cells as research tools and looking toward tissue engineering may close the uncertainty gaps between animal and human cross-species toxicology evaluations. The focus will be on developmental toxicology applications, but appropriate extrapolation to any other areas of toxicology can be made. We further provide background on basic biology of these three areas and examples of how early life exposure to known and potential environmental toxicants induce malformations, childhood and adult-onset diseases, through aberrant chromatin modification of critical gene expressions (acute lymphocyte leukemia, heavy-metal nickel and cadmium-associated defects, and reproductive tract malformations and carcinomas induced by the synthetic estrogen, diethylstilbestrol).
Cho
Elizabeth
E
Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. chofertikh@hotmail.com
Li
Wan-Ju
WJ
D000375:Aging; D000818:Animals; D002843:Chromatin / Q000187:drug effects*; D015509:Developmental Biology / Q000379:methods; D018628:Gene Dosage; D015870:Gene Expression / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D014116:Toxicology / Q000379:methods
D002843:Chromatin; D006657:Histones