Genotoxic damage of human adipose-tissue derived mesenchymal stem cells triggers their terminal differentiation

被引：18

作者：

Altanerova, V. ^{[1
]}

Horvathova, E. ^{[2
]}

Matuskova, M. ^{[1
]}

Kucerova, L. ^{[1
]}

Altaner, C. ^{[1
]}

机构：

[1] Canc Res Inst SAS, Mol Oncol Lab, Bratislava, Slovakia

[2] Canc Res Inst SAS, Lab Mutagenesis & Carcinogenesis, Bratislava, Slovakia

来源：

NEOPLASMA | 2009年 / 56卷 / 06期

关键词：

human adipose tissue-derived mesenchymal stem cells; genotoxic damage; single cell gel electrohoresis; chemical carcinogen 4NQO; terminal differentiation; BONE-MARROW; IN-VIVO; STROMAL CELLS; ALKALINE ELUTION; DNA LESIONS; CANCER; TRANSFORMATION; MURINE; LEADS;

D O I：

10.4149/neo_2009_06_542

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：542 / 547

页数：6

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