Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Identity, proliferation capacity, genomic stability and novel senescence markers of mesenchymal stem cells isolated from low volume of human bone marrow

Gabrielis Kundrotas _, Evelina Gasperskaja, Grazina Slapsyte, Zivile Gudleviciene, Jan Krasko, Ausra Stumbryte and Regina Liudkeviciene

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Oncotarget. 2016; 7:10788-10802. https://doi.org/10.18632/oncotarget.7456

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Abstract

Gabrielis Kundrotas1,2, Evelina Gasperskaja1, Grazina Slapsyte1, Zivile Gudleviciene2, Jan Krasko3, Ausra Stumbryte2 and Regina Liudkeviciene2

1 Department of Botany and Genetics, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania

2 Biobank, National Cancer Institute, Vilnius, Lithuania

3 Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania

Correspondence to:

Gabrielis Kundrotas, email:

Keywords: human mesenchymal stem cells, genomic stability, long-term expansion, PCR arrays, senescence markers, Gerotarget

Received: August 04, 2015 Accepted: February 05, 2016 Published: February 17, 2016

Abstract

Human bone marrow mesenchymal stem cells (hBM-MSCs) hold promise for treating incurable diseases and repairing of damaged tissues. However, hBM-MSCs face the disadvantages of painful invasive isolation and limited cell numbers. In this study we assessed characteristics of MSCs isolated from residual human bone marrow transplantation material and expanded to clinically relevant numbers at passages 3-4 and 6-7. Results indicated that early passage hBM-MSCs are genomically stable and retain identity and high proliferation capacity. Despite the chromosomal stability, the cells became senescent at late passages, paralleling the slower proliferation, altered morphology and immunophenotype. By qRT-PCR array profiling, we revealed 13 genes and 33 miRNAs significantly differentially expressed in late passage cells, among which 8 genes and 30 miRNAs emerged as potential novel biomarkers of hBM-MSC aging. Functional analysis of genes with altered expression showed strong association with biological processes causing cellular senescence. Altogether, this study revives hBM as convenient source for cellular therapy. Potential novel markers provide new details for better understanding the hBM-MSC senescence mechanisms, contributing to basic science, facilitating the development of cellular therapy quality control, and providing new clues for human disease processes since senescence phenotype of the hematological patient hBM-MSCs only very recently has been revealed.


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