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Transcriptional profiling of human mesenchymal stem cells transduced with reporter genes for imaging

Authors :
Yu Kuang
Nicolas Salem
Luis A. Solchaga
Joseph Molter
Zachary Love
Haibin Tian
Yunhui Kim
James E. Dennis
Fangjing Wang
Zhenghong Lee
Jeffery A. Kolthammer
Yuan Lin
Amad Awadallah
Stanton L. Gerson
Source :
Physiological Genomics. 37:23-34
Publication Year :
2009
Publisher :
American Physiological Society, 2009.

Abstract

Mesenchymal stem cells (MSCs) can differentiate into osteogenic, adipogenic, chondrogenic, myocardial, or neural lineages when exposed to specific stimuli, making them attractive for tissue repair and regeneration. We have used reporter gene-based imaging technology to track MSC transplantation or implantation in vivo. However, the effects of lentiviral transduction with the fluc-mrfp-ttk triple-fusion vector on the transcriptional profiles of MSCs remain unknown. In this study, gene expression differences between wild-type and transduced hMSCs were evaluated using an oligonucleotide human microarray. Significance Analysis of Microarray identified differential genes with high accuracy; RT-PCR validated the microarray results. Annotation analysis showed that transduced hMSCs upregulated cell differentiation and antiapoptosis genes while downregulating cell cycle, proliferation genes. Despite transcriptional changes associated with bone and cartilage remodeling, their random pattern indicates no systematic change of crucial genes that are associated with osteogenic, adipogenic, or chondrogenic differentiation. This correlates with the experimental results that lentiviral transduction did not cause the transduced MSCs to lose their basic stem cell identity as demonstrated by osteogenic, chondrogenic, and adipogenic differentiation assays with both transduced and wild-type MSCs, although a certain degree of alterations occurred. Histological analysis demonstrated osteogenic differentiation in MSC-loaded ceramic cubes in vivo. In conclusion, transduction of reporter genes into MSCs preserved the basic properties of stem cells while enabling noninvasive imaging in living animals to study the biodistribution and other biological activities of the cells.

Details

ISSN :
15312267 and 10948341
Volume :
37
Database :
OpenAIRE
Journal :
Physiological Genomics
Accession number :
edsair.doi.dedup.....247dae435804bef252f32f11fced0bb5
Full Text :
https://doi.org/10.1152/physiolgenomics.00300.2007