Cell Lines Derived from Human Parthenogenetic Embryos Can Display Aberrant Centriole Distribution and Altered Expression Levels of Mitotic Spindle Check-point Transcripts
Human parthenogenetic embryos have recently been proposed as an alternative, less controversial source of embryonic stem cell (ESC) lines; however many aspects related to the biology of parthenogenetic embryos and parthenogenetic derived cell lines still need to be elucidated. We present here result...
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Published in: | Stem cell reviews Vol. 5; no. 4; pp. 340 - 352 |
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01-12-2009
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Abstract | Human parthenogenetic embryos have recently been proposed as an alternative, less controversial source of embryonic stem cell (ESC) lines; however many aspects related to the biology of parthenogenetic embryos and parthenogenetic derived cell lines still need to be elucidated. We present here results on human cell lines (HP1 and HP3) derived from blastocysts obtained by oocyte parthenogenetic activation. Cell lines showed typical ESC morphology, expressed Oct-4, Nanog, Sox-2, Rex-1, alkaline phosphatase, SSEA-4, TRA 1-81 and had high telomerase activity. Expression of genes specific for different embryonic germ layers was detected from HP cells differentiated upon embryoid body (EBs) formation. Furthermore, when cultured in appropriate conditions, HP cell lines were able to differentiate into mature cell types of the neural and hematopoietic lineages. However, the injection of undifferentiated HP cells in immunodeficient mice resulted either in poor differentiation or in tumour formation with the morphological characteristics of myofibrosarcomas. Further analysis of HP cells indicated aberrant levels of molecules related to spindle formation as well as the presence of an abnormal number of centrioles and autophagic activity. Our results confirm and extend the notion that human parthenogenetic stem cells can be derived and can differentiate in mature cell types, but also highlight the possibility that, alteration of the proliferation mechanisms may occur in these cells, suggesting great caution if a therapeutic use of this kind of stem cells is considered. |
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AbstractList | Human parthenogenetic embryos have recently been proposed as an alternative, less controversial source of embryonic stem cell (ESC) lines; however many aspects related to the biology of parthenogenetic embryos and parthenogenetic derived cell lines still need to be elucidated. We present here results on human cell lines (HP1 and HP3) derived from blastocysts obtained by oocyte parthenogenetic activation. Cell lines showed typical ESC morphology, expressed Oct-4, Nanog, Sox-2, Rex-1, alkaline phosphatase, SSEA-4, TRA 1-81 and had high telomerase activity. Expression of genes specific for different embryonic germ layers was detected from HP cells differentiated upon embryoid body (EBs) formation. Furthermore, when cultured in appropriate conditions, HP cell lines were able to differentiate into mature cell types of the neural and hematopoietic lineages. However, the injection of undifferentiated HP cells in immunodeficient mice resulted either in poor differentiation or in tumour formation with the morphological characteristics of myofibrosarcomas. Further analysis of HP cells indicated aberrant levels of molecules related to spindle formation as well as the presence of an abnormal number of centrioles and autophagic activity. Our results confirm and extend the notion that human parthenogenetic stem cells can be derived and can differentiate in mature cell types, but also highlight the possibility that, alteration of the proliferation mechanisms may occur in these cells, suggesting great caution if a therapeutic use of this kind of stem cells is considered. |
Author | Rebulla, Paolo Scanziani, Eugenio Tettamanti, Gianluca Pennarossa, Georgia Antonini, Stefania Radaelli, Enrico de Eguileor, Magda Lazzari, Lorenza Ragni, Guido Brevini, Tiziana A. L. Paffoni, Alessio Gandolfi, Fulvio Benvenisty, Nissim Montemurro, Tiziana |
Author_xml | – sequence: 1 givenname: Tiziana A. L. surname: Brevini fullname: Brevini, Tiziana A. L. email: tiziana.brevini@unimi.it organization: Laboratory of Biomedical Embryology, Centre for Stem Cell Research, University of Milan – sequence: 2 givenname: Georgia surname: Pennarossa fullname: Pennarossa, Georgia organization: Laboratory of Biomedical Embryology, Centre for Stem Cell Research, University of Milan, National Institute of Molecular Genetics (INGM) – sequence: 3 givenname: Stefania surname: Antonini fullname: Antonini, Stefania organization: Laboratory of Biomedical Embryology, Centre for Stem Cell Research, University of Milan – sequence: 4 givenname: Alessio surname: Paffoni fullname: Paffoni, Alessio organization: Infertility Unit, Department of Obstetrics, Gynaecology and Neonatology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena – sequence: 5 givenname: Gianluca surname: Tettamanti fullname: Tettamanti, Gianluca organization: Department of Biotechnology and Molecular Sciences, University of Insubria – sequence: 6 givenname: Tiziana surname: Montemurro fullname: Montemurro, Tiziana organization: Cell Factory ‘Franco Calori’, Center of Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena – sequence: 7 givenname: Enrico surname: Radaelli fullname: Radaelli, Enrico organization: Department of Veterinary Pathology, Hygiene and Public Health, University of Milan – sequence: 8 givenname: Lorenza surname: Lazzari fullname: Lazzari, Lorenza organization: Cell Factory ‘Franco Calori’, Center of Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena – sequence: 9 givenname: Paolo surname: Rebulla fullname: Rebulla, Paolo organization: Cell Factory ‘Franco Calori’, Center of Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena – sequence: 10 givenname: Eugenio surname: Scanziani fullname: Scanziani, Eugenio organization: Department of Veterinary Pathology, Hygiene and Public Health, University of Milan – sequence: 11 givenname: Magda surname: de Eguileor fullname: de Eguileor, Magda organization: Department of Biotechnology and Molecular Sciences, University of Insubria – sequence: 12 givenname: Nissim surname: Benvenisty fullname: Benvenisty, Nissim organization: Stem Cells Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University – sequence: 13 givenname: Guido surname: Ragni fullname: Ragni, Guido organization: Infertility Unit, Department of Obstetrics, Gynaecology and Neonatology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena – sequence: 14 givenname: Fulvio surname: Gandolfi fullname: Gandolfi, Fulvio organization: Laboratory of Biomedical Embryology, Centre for Stem Cell Research, University of Milan |
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Keywords | Human Parthenogenetic cell lines Mitotic check-point transcripts Centriole |
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Snippet | Human parthenogenetic embryos have recently been proposed as an alternative, less controversial source of embryonic stem cell (ESC) lines; however many aspects... |
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SubjectTerms | Adult Animals Biomedical and Life Sciences Biomedical Engineering and Bioengineering Cell Biology Cell Differentiation Cells, Cultured Centrioles - metabolism Centrioles - ultrastructure Embryo, Mammalian - cytology Embryo, Mammalian - metabolism Female Gene Expression Regulation, Developmental Humans Life Sciences Mice Microscopy, Electron Parthenogenesis Regenerative Medicine/Tissue Engineering Spindle Apparatus - metabolism Stem Cells Transcription, Genetic |
Title | Cell Lines Derived from Human Parthenogenetic Embryos Can Display Aberrant Centriole Distribution and Altered Expression Levels of Mitotic Spindle Check-point Transcripts |
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