Amniotic fluid skin cells can be safely obtained from pregnant women undergoing amniocentesis at about 15 weeks of pregnancy as part of a diagnostic workup for chromosome aberrations and other genetic diseases. About 99 percent of cells found in amniotic fluid are terminally differentiated cells mostly from fetal skin, which are shed into the amniotic fluid as a fetus develops. Since these cells can be reprogrammed to pluripotency more efficiently than other cell types, they could be an important source for generating stem cells for basic research and future therapies and may be used to study and potentially cure fatal embryonic diseases with prenatal, perinatal gene therapy.
“We induced amniotic fluid skin cells to return from their final differentiated stage back to an undifferentiated stem cell stage from where they can develop into any cell type of the body,” said Dr. Polgar. “Amniotic fluid cells work much better than any other cell types when turning back their ‘internal clock.’ These cells can potentially be used as a model system in studying different regenerative therapies for diseases of the heart, liver, kidney, lung, pancreas, as well as for replacement of lost neurons in Alzheimer’s, Parkinson’s, even for cancer vaccines. They may also be used for future personalized stem cell banks. As the pluripotent stem cells induced from amniotic fluid skin cells are the patient’s own cells, there is no risk of immunorejection or teratocarcinoma formation.
The scientists were able to genetically reprogram the amniotic fluid skin cells using the four transcription factors (proteins that regulate the transcription of genes) OCT3/4, SOX2, KLF4, and c-MYC. After reprogramming, the cells were found to be identical to human embryonic stem cells in numerous ways, including for morphological and growth characteristics, antigenic stem cell markers, stem cell gene expression, and telomerase activity, in vitro and in vivo differentiation.
In addition to Dr. Katalin Polgar, co-authors of the paper include: Valentin Fuster, MD, PhD, Director, Mount Sinai Heart, the Zena and Michael A. Wiener Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Center for Cardiovascular Health; Roger Hajjar, MD, Professor, Director of the Cardiovascular Research Center, Mount Sinai School of Medicine; Robert J. Desnick, MD, PhD, Professor and Chair of the Department of Genetics and Genomic Sciences, Dean for Genetics and Genomics, Mount Sinai School of Medicine; Michael Brodman, MD, Professor and Chair Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine.
The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation’s oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 60,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center.