title: Early spontaneous immortalization and loss of plasticity of rabbit bone marrow mesenchymal stem cells.
abstract: OBJECTIVE
  Bone marrow-derived mesenchymal stem cells (BM-MSC) have been widely used for cell therapy and tissue engineering purposes. However, there are still controversies concerning safety of application of these cells after in vitro expansion. Therefore, we aimed to investigate the characteristics of rabbit BM-MSC during long-term culture.
  
  
  METHODS
  In this study, we have examined growth kinetics, morphological changes, differentiation potential and chromosomal abnormalities, as well as tumour formation potential of rabbit BM-MSC in long-term culture.
  
  
  CONCLUSIONS
  We found that shortly after isolation, proliferation rate of rabbit BM-MSC decreases until they enter a dormant phase. During this period of quiescence, the cells are large and multinucleate. After some weeks of dormancy we found that several small mononuclear cells originated from each large multinucleate cell. These newly formed cells proliferated rapidly but had inferior differentiation potential. Although they were immortal, they did not have the capability for tumour formation in soft agar assay or in nude mice. This is the first report of spontaneous, non-tumorigenic immortalization of BM-MSC in rabbits. The phenomenon raises more concern for meticulous monitoring and quality control for using rabbit BM-MSC in cell-based therapies and tissue engineering experiments.
authors.affiliation: Stem Cell Biology Department, Stem Cell Technology Research Center, Tehran, Iran.
authors.forename: N
authors.initials: N
authors.lastname: Ahmadbeigi
authors.forename: A
authors.initials: A
authors.lastname: Shafiee
authors.forename: E
authors.initials: E
authors.lastname: Seyedjafari
authors.forename: Y
authors.initials: Y
authors.lastname: Gheisari
authors.forename: M
authors.initials: M
authors.lastname: Vassei
authors.forename: S
authors.initials: S
authors.lastname: Amanpour
authors.forename: S
authors.initials: S
authors.lastname: Amini
authors.forename: I
authors.initials: I
authors.lastname: Bagherizadeh
authors.forename: M
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D011817:Rabbits; D013997:Time Factors