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
Main Authors: Brevini, Tiziana A. L., Pennarossa, Georgia, Antonini, Stefania, Paffoni, Alessio, Tettamanti, Gianluca, Montemurro, Tiziana, Radaelli, Enrico, Lazzari, Lorenza, Rebulla, Paolo, Scanziani, Eugenio, de Eguileor, Magda, Benvenisty, Nissim, Ragni, Guido, Gandolfi, Fulvio
Format: Journal Article
Language:English
Published: New York Humana Press Inc 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.
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
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  givenname: Lorenza
  surname: Lazzari
  fullname: Lazzari, Lorenza
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  givenname: Paolo
  surname: Rebulla
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  givenname: Fulvio
  surname: Gandolfi
  fullname: Gandolfi, Fulvio
  organization: Laboratory of Biomedical Embryology, Centre for Stem Cell Research, University of Milan
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Parthenogenetic cell lines
Mitotic check-point transcripts
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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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StartPage 340
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
URI https://link.springer.com/article/10.1007/s12015-009-9086-9
https://www.ncbi.nlm.nih.gov/pubmed/20058199
Volume 5
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