Genotoxic damage of human adipose-tissue derived mesenchymal stem cells triggers their terminal differentiation.
Human adipose tissue-derived mesenchymal (stromal) stem cells (AT-MSCs) and genetically modified to express cytosine deaminase:uracil phosphoribosyltransferase (CDy-AT-MSCs) were treated with hydrogen peroxide in order to induce DNA damage and subsequently evaluate their genetic stability by single cell gel electrophoresis. Both cells types (parental and transgene modified) did not differ in the sensitivity to DNA breaks induction. Potential tumorigenicity of AT-MSCs and CDy-AT-MSCs was tested by subcutaneous inoculation of cell suspension into flank of immunocompromised mice. Dose of 15x10(6) cells was not found to be tumorigenic in given experimental setup. AT-MSCs, CDy-AT-MSCs and MSCs isolated from human lipoma were treated with chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) in attempts to transform them. Surviving cells after genotoxic stress were not transformed but underwent replicative senescence. Irreparable DNA damage caused triggered adipogenic terminal differentiation, rather than apoptosis induction in all kinds of cells tested.
Altanerova
V
V
Laboratory of Molecular Oncology, Cancer Research Institute, Bratislava, Slovakia. exonalt@savba.sk
Horvathova
E
E
Matuskova
M
M
Kucerova
L
L
Altaner
C
C
D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D016922:Cellular Senescence; D043525:Cytosine Deaminase / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008067:Lipoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D016877:Oxidants / Q000494:pharmacology; D010430:Pentosyltransferases / Q000235:genetics; D019076:Transgenes / Q000502:physiology
D016877:Oxidants; D006861:Hydrogen Peroxide; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D043525:Cytosine Deaminase