Stem Cell Characteristics of Amniotic Epithelial Cells

Amniotic epithelial cells develop from the epiblast by 8 days after fertilization and before gastrulation, opening the possibility that they might maintain the plasticity of pregastrulation embryo cells. Here we show that amniotic epithelial cells isolated from human term placenta express surface markers normally present on embryonic stem and germ cells. In addition, amniotic epithelial cells express the pluripotent stem cell–specific transcription factors octamer‐binding protein 4 (Oct‐4) and nanog. Under certain culture conditions, amniotic epithelial cells form spheroid structures that retain stem cell characteristics. Amniotic epithelial cells do not require other cell‐derived feeder layers to maintain Oct‐4 expression, do not express telomerase, and are nontumorigenic upon transplantation. Based on immunohistochemical and genetic analysis, amniotic epithelial cells have the potential to differentiate to all three germ layers—endoderm (liver, pancreas), mesoderm (cardiomyocyte), and ectoderm (neural cells) in vitro. Amnion derived from term placenta after live birth may be a useful and noncontroversial source of stem cells for cell transplantation and regenerative medicine.

[1]  N. Sakuragawa,et al.  Evidence for synthesis and release of catecholamines by human amniotic epithelial cells , 1997, Neuroreport.

[2]  E. Parati,et al.  Isolation and Cloning of Multipotential Stem Cells from the Embryonic Human CNS and Establishment of Transplantable Human Neural Stem Cell Lines by Epigenetic Stimulation , 1999, Experimental Neurology.

[3]  M. Sasaki,et al.  Amniotic tissue transplantation: Clinical and biochemical evaluations for some lysosomal storage diseases , 1992, Brain and Development.

[4]  S. Bonner-Weir,et al.  In vitro cultivation of human islets from expanded ductal tissue. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[6]  L. C. Stevens,et al.  Development of teratomas from the ectoderm of mouse egg cylinders. , 1976, Journal of the National Cancer Institute.

[7]  A. Tylki-Szymańska,et al.  Amniotic tissue transplantation as a trial of treatment in some lysosomal storage diseases , 1985, Journal of Inherited Metabolic Disease.

[8]  K. Miyamoto,et al.  Human Placenta Feeder Layers Support Undifferentiated Growth of Primate Embryonic Stem Cells , 2004, Stem cells.

[9]  T. Itakura,et al.  Human Amniotic Epithelial Cells Produce Dopamine and Survive after Implantation into the Striatum of a Rat Model of Parkinson's Disease: A Potential Source of Donor for Transplantation Therapy , 2000, Experimental Neurology.

[10]  Pratima Kundu,et al.  Generation of Hepatocyte-Like Cells from Human Embryonic Stem Cells , 2003, Cell transplantation.

[11]  J. Miyazaki,et al.  Phenotypic Complementation Establishes Requirements for Specific POU Domain and Generic Transactivation Function of Oct-3/4 in Embryonic Stem Cells , 2002, Molecular and Cellular Biology.

[12]  R. Thangavel,et al.  Expression of markers for both neuronal and glial cells in human amniotic epithelial cells , 1996, Neuroscience Letters.

[13]  J. Rossant,et al.  Promotion of trophoblast stem cell proliferation by FGF4. , 1998, Science.

[14]  J. Sahi,et al.  Effects of bergamottin on human and monkey drug-metabolizing enzymes in primary cultured hepatocytes. , 2002, Drug metabolism and disposition: the biological fate of chemicals.

[15]  Y. Romanov,et al.  Searching for Alternative Sources of Postnatal Human Mesenchymal Stem Cells: Candidate MSC‐Like Cells from Umbilical Cord , 2003, Stem cells.

[16]  F. Claas,et al.  Isolation of Mesenchymal Stem Cells of Fetal or Maternal Origin from Human Placenta , 2004, Stem cells.

[17]  T. Nikaido,et al.  Human Amnion-Isolated Cells Normalize Blood Glucose in Streptozotocin-Induced Diabetic Mice , 2003, Cell transplantation.

[18]  F. Gage,et al.  Setting Standards for Human Embryonic Stem Cells , 2003, Science.

[19]  Andrea-Romana Prusa,et al.  Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research? , 2003, Human reproduction.

[20]  H. Moser,et al.  A therapeutic trial of amniotic epithelial cell implantation in patients with lysosomal storage diseases. , 1985, American journal of medical genetics.

[21]  Kenji Takahashi,et al.  Effects of Osteogenic Induction on Mesenchymal Cells from Fetal and Maternal Parts of Human Placenta , 2004, Cell transplantation.

[22]  G. Michalopoulos,et al.  Hepatic oval cells express the hematopoietic stem cell marker thy‐1 in the rat , 1998, Hepatology.

[23]  F. Claas,et al.  Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. , 2003, Blood.

[24]  T. F. O'Brien,et al.  Multipotent Stem/Progenitor Cells with Similar Properties Arise from Two Neurogenic Regions of Adult Human Brain , 1999, Experimental Neurology.

[25]  P. Wernet,et al.  A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential , 2004, The Journal of experimental medicine.

[26]  Toshio Miki,et al.  Use and application of stem cells in toxicology. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[27]  J. Thomson,et al.  Preimplantation Human Embryos and Embryonic Stem Cells Show Comparable Expression of Stage‐Specific Embryonic Antigens , 2002, Stem cells.

[28]  A. Trounson,et al.  Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro , 2000, Nature Biotechnology.

[29]  H. Yamamoto,et al.  Immunostaining of human amniotic epithelial cells: possible use as a transgene carrier in gene therapy for inborn errors of metabolism. , 1995, Cell transplantation.

[30]  Naohiro Terada,et al.  Embryoid‐body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes , 2002, Hepatology.

[31]  T. Kitamura,et al.  Human Placenta‐Derived Cells Have Mesenchymal Stem/Progenitor Cell Potential , 2004, Stem cells.

[32]  M. Murakami,et al.  The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells , 2003, Cell.

[33]  B. Scaggiante,et al.  Successful therapy of Niemann-Pick disease by implantation of human amniotic membrane. , 1987, Transplantation.

[34]  R. Thangavel,et al.  Human amniotic epithelial cells are promising transgene carriers for allogeneic cell transplantation into liver , 2000, Journal of Human Genetics.

[35]  Linzhao Cheng,et al.  Human Adult Marrow Cells Support Prolonged Expansion of Human Embryonic Stem Cells in Culture , 2003, Stem cells.

[36]  S. Leibowitz,et al.  IMMUNOGENICITY OF HUMAN AMNIOTIC EPITHELIAL CELLS AFTER TRANSPLANTATION INTO VOLUNTEERS , 1981, The Lancet.

[37]  S. Thorgeirsson,et al.  Coexpression of stem cell factor and c-kit in embryonic and adult liver. , 1996, Experimental cell research.

[38]  D. Kooy,et al.  Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations , 2002, Nature Medicine.

[39]  J. Nichols,et al.  Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem Cells , 2003, Cell.