TY - JOUR
T1 - Cell lines derived from human parthenogenetic embryos can display aberrant centriole distribution and altered expression levels of mitotic spindle check-point transcripts
AU - Brevini, Tiziana A.L.
AU - Pennarossa, Georgia
AU - Antonini, Stefania
AU - Paffoni, Alessio
AU - Tettamanti, Gianluca
AU - Montemurro, Tiziana
AU - Radaelli, Enrico
AU - Lazzari, Lorenza
AU - Rebulla, Paolo
AU - Scanziani, Eugenio
AU - de Eguileor, Magda
AU - Benvenisty, Nissim
AU - Ragni, Guido
AU - Gandolfi, Fulvio
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - Centriole
KW - Human
KW - Mitotic check-point transcripts
KW - Parthenogenetic cell lines
UR - http://www.scopus.com/inward/record.url?scp=74649084501&partnerID=8YFLogxK
U2 - 10.1007/s12015-009-9086-9
DO - 10.1007/s12015-009-9086-9
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C2 - 20058199
AN - SCOPUS:74649084501
SN - 1550-8943
VL - 5
SP - 340
EP - 352
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
IS - 4
ER -