Therapeutic gene expression in transduced mesenchymal stem cells can be monitored using a reporter gene

Magnetic resonance imaging (MRI) based on the ferritin heavy chain 1 (FTH1) reporter gene has been used to trace stem cells. However, whether FTH1 expression is affected by stem cell differentiation or whether cell differentiation is affected by reporter gene expression remains unclear. Here, we explore the relationship between FTH1 expression and neural differentiation in the differentiation of mesenchymal stem cells (MSCs) carrying FTH1 into neuron-like cells and investigate the feasibility of using FTH1 as an MRI reporter gene to detect neurally differentiated cells. By inducing cell differentiation with all-trans retinoic acid and a modified neuronal medium, MSCs and MSCs-FTH1 were successfully differentiated into neuron-like cells (Neurons and Neurons-FTH1), and the neural differentiation rates were (91.56±7.89)% and (92.23±7.64)%, respectively. Neuron-specific markers, including nestin, neuron-specific enolase, and microtubule-associated protein-2, were significantly expressed in Neurons-FTH1 and Neurons without noticeable differences. On the other hand, FTH1 was significantly expressed in MSCs-FTH1 and Neurons-FTH1 cells, and the expression levels were not significantly different. The R2 value was significantly increased in MSCs-FTH1 and Neurons-FTH1 cells, which was consistent with the findings of Prussian blue staining, transmission electron microscopy, and intracellular iron measurements. These results suggest that FTH1 gene expression did not affect MSC differentiation into neurons and was not affected by neural differentiation. Thus, MRI reporter gene imaging based on FTH1 can be used for the detection of neurally differentiated cells from MSCs.

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Serial Noninvasive In Vivo Positron Emission Tomographic Tracking of Percutaneously Intramyocardially Injected Autologous Porcine Mesenchymal Stem Cells Modified for Transgene Reporter Gene Expression

Circulation Cardiovascular Imaging ◽

10.1161/circimaging.108.797449 ◽

2008 ◽

Vol 1 (2) ◽

pp. 94-103 ◽

Cited By ~ 105

Author(s):

Mariann Gyöngyösi ◽

Jeronimo Blanco ◽

Teréz Marian ◽

Lajos Trón ◽

Örs Petneházy ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Reporter Gene ◽

Reporter Gene Expression ◽

Positron Emission Tomographic ◽

Positron Emission

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A Gold Nanoparticle Pentapeptide: Gene Fusion To Induce Therapeutic Gene Expression in Mesenchymal Stem Cells

Journal of the American Chemical Society ◽

10.1021/ja505190q ◽

2014 ◽

Vol 136 (42) ◽

pp. 14763-14771 ◽

Cited By ~ 28

Author(s):

Megan E. Muroski ◽

Thomas J. Morgan ◽

Cathy W. Levenson ◽

Geoffrey F. Strouse

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Gold Nanoparticle ◽

Gene Fusion ◽

Therapeutic Gene

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Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis

Journal of Bone and Mineral Research ◽

10.1002/jbmr.460 ◽

2011 ◽

Vol 26 (10) ◽

pp. 2552-2563 ◽

Cited By ~ 166

Author(s):

Pei-Chi Tseng ◽

Sheng-Mou Hou ◽

Ruey-Jien Chen ◽

Hsiao-Wen Peng ◽

Chi-Fen Hsieh ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells

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Modulation of Human Mesenchymal Stem Cells by Electrical Stimulation Using an Enzymatic Biofuel Cell

Catalysts ◽

10.3390/catal11010062 ◽

2021 ◽

Vol 11 (1) ◽

pp. 62

Author(s):

Won-Yong Jeon ◽

Seyoung Mun ◽

Wei Beng Ng ◽

Keunsoo Kang ◽

Kyudong Han ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Electrical Stimulation ◽

Regenerative Medicine ◽

Cell Morphology ◽

Electrical Current ◽

Specific Gene ◽

Next Generation ◽

The Impact

Enzymatic biofuel cells (EBFCs) have excellent potential as components in bioelectronic devices, especially as active biointerfaces to regulate stem cell behavior for regenerative medicine applications. However, it remains unclear to what extent EBFC-generated electrical stimulation can regulate the functional behavior of human adipose-derived mesenchymal stem cells (hAD-MSCs) at the morphological and gene expression levels. Herein, we investigated the effect of EBFC-generated electrical stimulation on hAD-MSC cell morphology and gene expression using next-generation RNA sequencing. We tested three different electrical currents, 127 ± 9, 248 ± 15, and 598 ± 75 nA/cm2, in mesenchymal stem cells. We performed transcriptome profiling to analyze the impact of EBFC-derived electrical current on gene expression using next generation sequencing (NGS). We also observed changes in cytoskeleton arrangement and analyzed gene expression that depends on the electrical stimulation. The electrical stimulation of EBFC changes cell morphology through cytoskeleton re-arrangement. In particular, the results of whole transcriptome NGS showed that specific gene clusters were up- or down-regulated depending on the magnitude of applied electrical current of EBFC. In conclusion, this study demonstrates that EBFC-generated electrical stimulation can influence the morphological and gene expression properties of stem cells; such capabilities can be useful for regenerative medicine applications such as bioelectronic devices.

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MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta

Scientific Reports ◽

10.1038/s41598-021-87298-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kulisara Marupanthorn ◽

Chairat Tantrawatpan ◽

Pakpoom Kheolamai ◽

Duangrat Tantikanlayaporn ◽

Sirikul Manochantr

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Transcription Factor ◽

Osteogenic Differentiation ◽

Differentiation Potential ◽

Osteogenic Gene Expression ◽

Osteogenic Gene

AbstractMesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.

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