Parthenogenetic Cell Lines: An Unstable Equilibrium Between Pluripotency and Malignant Transformation

Tiziana      A.L. Brevini; Georgia      Pennarossa; Magda      de Eguileor; Gianluca      Tettamanti; Guido      Ragni; Alessio      Paffoni; Fulvio      Gandolfi

Abstract

Human parthenogenetic embryos have been recently proposed as an alternative, less controversial source of embryonic stem cells. However many aspects related to the biology of parthenogenetic cell lines are not fully understood and still need to be elucidated. These cells have great potentials; they possess most of the main features of bi-parental stem cells, show the typical morphology and express most of the pluripotency markers distinctive of ESC. They also have high telomerase activity, that disappears upon differentiation, and display great plasticity. When cultured in appropriate conditions, they are able to give rise to high specification tissues and to differentiate into mature cell types of the neural and hematopoietic lineages. However, their injection in immunodeficient mice has been reported to result in tumour formations. Aberrant levels of molecules related to spindle formation, cell cycle check points and chromosome segregation have also been detected in these cells, that are characterized by the presence of an abnormal number of centrioles and massive autophagy. All these observations indicate the presence of an intrinsic deregulation of the mechanisms controlling proliferation versus differentiation in parthenogenetic stem cells. In this manuscript we summarize data related to these aberrant controls and describe experimental evidence indicating their uniparental origin as one of the possible cause. Finally we propose their use as an intriguing experimental tool where the pathways controlling potency, self renewal and cell plasticity are deeply interconnected with cell transformation, in an unstable, although highly controlled, equilibrium between pluripotency and malignacy.

Keywords: Centriole, mitotic spindle, parthenogenesis, pluripotency, tumorigenic, Malignant Transformation, embryonic stem cells, telomerase activity, hematopoietic lineages, cell cycle check points, chromosome, massive autophagy, proliferation, oocyte, parthenogenetic embryos, Parthenotes, embryonic centrosome, bi-parental embryonic stem cells, blastocyst, alkaline phosphatase, embryoid bodies (EBs), trofectoderm-related markers, murine, cytokines, lymphoid, erythroid, myeloid, malignant sarcomas, myofibroblastic differentiation, oogenesis, oogonia, spermatozoon, mixoploid chromosomal, mitosis, autophagocitic activity, kinetochore-microtubule binding, apoptosis, centrosome, aneuploidy, Drosophila mutants