Anat Cell Biol.  2014 Dec;47(4):217-226. 10.5115/acb.2014.47.4.217.

Microarray analysis after umbilical cord blood derived mesenchymal stem cells injection in monocrotaline-induced pulmonary artery hypertension rats

• Lee JC
• Kim KC
• Yang YS
• Oh W
• Choi SJ
• Choe SY
• Hong YM

• KMID: 1882600
• DOI: http://doi.org/10.5115/acb.2014.47.4.217

Abstract

Pulmonary arterial hypertension (PAH) is associated with structural alterations of lung vasculature. PAH is still a devastating disease needing an aggressive therapeutic approach. Despite the therapeutic potential of human umbilical cord mesenchymal stem cells (MSCs), the molecular parameters to define the stemness remain largely unknown. Using high-density oligonucleotide microarrays, the differential gene expression profiles between a fraction of mononuclear cells of human umbilical cord blood (UCB) and its MSC subpopulation were obtained. Of particular interest was a subset of 46 genes preferentially expressed at 7-fold or higher in the group treated with human UCB-MSCs. This subset contained numerous genes involved in the inflammatory response, immune response, lipid metabolism, cell adhesion, cell migration, cell differentiation, apoptosis, cell growth, transport, cell proliferation, transcription, and signal transduction. Our results provide a foundation for a more reproducible and reliable quality control using genotypic analysis for the definition of human UCB-MSCs. Therefore, our results will provide a basis for studies on molecular mechanisms controlling the core properties of human MSCs.

Keyword

Pulmonary hypertension; Monocrotaline; Umbilical mesenchymal stem cells; Microarray

MeSH Terms

Animals
Apoptosis
Cell Adhesion
Cell Differentiation
Cell Movement
Cell Proliferation
Fetal Blood*
Humans
Hypertension*
Hypertension, Pulmonary
Lipid Metabolism
Lung
Mesenchymal Stromal Cells*
Microarray Analysis*
Monocrotaline
Oligonucleotide Array Sequence Analysis
Pulmonary Artery*
Quality Control
Rats*
Signal Transduction
Transcriptome
Umbilical Cord
Monocrotaline

Figure

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  Fig. 1 Human umbilical cord blood (UCB)-mesenchymal stem cell (MSCs) preparation. Characterization of human UCB-MSCs at passage 5 (A-D). Immunophenotype from human UCB-MSCs. These cells positive for antigens CD73 and CD105 but generally not for antigens CD14 and CD34 but generally not for. The gray lines indicate the isotype matched mouse IgG antibody control labeling (A, B, negative for the surface markers; C, D, positive for the surface markers.).

• 

  Fig. 2 The intensity plot demonstrate the consistency and correction of these array experiments (A-C). The expression profiles from the M group and U group were compared with those of the reference C group. The genes in which the detected signal showed a more than 2-fold difference between the samples fall outside of thin lines near the center of the scatterplot, respectively. C, control group; M, monocrotaline group; U, human umbilical cord blood-mesenchymal stem cells group.

• 

  Fig. 3 The M versus A plot. M versus A plot showing genes identified as differentially expressed (2-fold or more, P≤0.05) between U, M, and C group between the samples fall outside of thin lines near the center of the scatterplot, respectively (A, B). C, control group; M, monocrotaline group; U, human umbilical cord blood-mesenchymal stem cells group.

• 

  Fig. 4 Gene heat map in pulmonary arterial hypertension (PAH) rats and human umbilical cord blood (UCB)-mesenchymal stem cells (MSCs) injection. The expression profiles of heat shock-activated genes were clustered hierarchically and are displayed using a red-green heat map. Heat map of genes upregulated and down-regulated ≥2 fold in PAH rats and human UCB-MSCs injection. The color red indicates over expression while green indicates down expression. C, control group; M, monocrotaline group; U, human UCB-MSCs group.

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