title: Dormant phase and multinuclear cells: two key phenomena in early culture of murine bone marrow mesenchymal stem cells.
abstract: Special features of mesenchymal stem cells (MSCs) have made them a popular tool in cell therapy and tissue engineering. Although mouse animal models and murine MSCs are common tools in this field, our understanding of the effect of in vitro expansion on the behavior of these cells is poor and controversial. In addition, in comparison to human, isolation of MSCs from mouse has been reported to be more difficult and some unexplained features such as heterogeneity and slow growth rate in the culture of these cells have been observed. Here we followed mouse bone marrow MSCs for >1 year after isolation and examined the effect of expansion on changes in morphology, growth kinetics, plasticity, and chromosomal structure during in vitro culture. Shortly after isolation, the growth rate of the cells decreased until they stopped dividing and entered a dormant state. In this state the size of the cells increased and they became multinuclear. These large multinuclear cells then gave origin to small mononuclear cells, which after a while resumed proliferation and could be expanded immortally. The immortal cells had diminished plasticity and were aneuploid but could not form tumors in nude mice. These results suggest that mouse bone marrow MSCs bear several modifications when expanded in vitro, and therefore, the interpretation of the data obtained with these cells should be done more cautiously.
authors.affiliation: Department of Stem Cell Biology and Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Ahmadbeigi
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.forename: Yousof
authors.initials: Y
authors.lastname: Gheisari
authors.forename: Mohammad
authors.initials: M
authors.lastname: Vasei
authors.forename: Saeid
authors.initials: S
authors.lastname: Amanpour
authors.forename: Iman
authors.initials: I
authors.lastname: Bagherizadeh
authors.forename: Seyed Ali Mohammad
authors.initials: SA
authors.lastname: Shariati
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
authors.forename: Sepideh
authors.initials: S
authors.lastname: Amini
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.forename: Vahid
authors.initials: V
authors.lastname: Arabkari
authors.forename: Nance Beyer
authors.initials: NB
authors.lastname: Nardi
mesh_terms: D000818:Animals; D000954:Antigens, Surface; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002875:Chromosomes; D004247:DNA / Q000032:analysis / Q000235:genetics; D015726:Giant Cells / Q000166:cytology*; D059785:Karyotype; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D000954:Antigens, Surface; D004247:DNA