Low-Intensity Ultrasound Upregulates the Expression of Cyclin-D1 and Promotes Cellular Proliferation in Human Mesenchymal Stem Cells

Gaurav Budhiraja, Neety Sahu, Anuradha Subramanian

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2 Citations (Scopus)

Abstract

Human mesenchymal stem cells (hMSCs) hold great potential for cellular based therapeutics and tissue engineering applications and their expansion is an interesting prospect due to their low availability from in vivo sources. Therefore, this study investigated the effect of continuous-wave low-intensity ultrasound (LIUS) at 5.0-MHz and 14.0-kPa (<20mWcm-2) on the proliferative capacity, colony-formation efficiency, genetic stability, and differentiation potential of hMSCs. Additionally, potential signaling pathways involved in LIUS-mediated proliferation of hMSCs are studied. Compared to non-stimulated controls, LIUS-treated hMSCs shows a 1.9-fold greater colony-forming efficiency and 2.5-fold higher rate of cell proliferation, respectively. Differential staining and qRT-PCR analysis for selective chondrogenic, osteogenic, and adipogenic markers further confirmed that the LIUS treatment did not impact the multipotency of hMSCs. LIUS-treated hMSCs expressed normal male karyotype. The synthesis of cyclin-D1, a master regulator of cellular proliferation, is upregulated under LIUS and its enhanced mRNA expression under LIUS is noted to be mediated by the activation of both MAPK/ERK and PI3K/AKT pathways. In conclusion, LIUS promotes proliferation and self-renewal capacity of hMSCs.

Original languageEnglish (US)
JournalBiotechnology Journal
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Cyclin D1
Mesenchymal Stromal Cells
Up-Regulation
Cell Proliferation
Tissue Engineering
Phosphatidylinositol 3-Kinases
Karyotype
Staining and Labeling
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Cell proliferation
  • Cyclin-D1
  • Extracellular signal-regulated kinases (ERK)
  • Mesenchymal stem cells
  • Ultrasound (US)

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Molecular Medicine

Cite this

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title = "Low-Intensity Ultrasound Upregulates the Expression of Cyclin-D1 and Promotes Cellular Proliferation in Human Mesenchymal Stem Cells",
abstract = "Human mesenchymal stem cells (hMSCs) hold great potential for cellular based therapeutics and tissue engineering applications and their expansion is an interesting prospect due to their low availability from in vivo sources. Therefore, this study investigated the effect of continuous-wave low-intensity ultrasound (LIUS) at 5.0-MHz and 14.0-kPa (<20mWcm-2) on the proliferative capacity, colony-formation efficiency, genetic stability, and differentiation potential of hMSCs. Additionally, potential signaling pathways involved in LIUS-mediated proliferation of hMSCs are studied. Compared to non-stimulated controls, LIUS-treated hMSCs shows a 1.9-fold greater colony-forming efficiency and 2.5-fold higher rate of cell proliferation, respectively. Differential staining and qRT-PCR analysis for selective chondrogenic, osteogenic, and adipogenic markers further confirmed that the LIUS treatment did not impact the multipotency of hMSCs. LIUS-treated hMSCs expressed normal male karyotype. The synthesis of cyclin-D1, a master regulator of cellular proliferation, is upregulated under LIUS and its enhanced mRNA expression under LIUS is noted to be mediated by the activation of both MAPK/ERK and PI3K/AKT pathways. In conclusion, LIUS promotes proliferation and self-renewal capacity of hMSCs.",
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author = "Gaurav Budhiraja and Neety Sahu and Anuradha Subramanian",
year = "2018",
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AU - Budhiraja, Gaurav

AU - Sahu, Neety

AU - Subramanian, Anuradha

PY - 2018/1/1

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N2 - Human mesenchymal stem cells (hMSCs) hold great potential for cellular based therapeutics and tissue engineering applications and their expansion is an interesting prospect due to their low availability from in vivo sources. Therefore, this study investigated the effect of continuous-wave low-intensity ultrasound (LIUS) at 5.0-MHz and 14.0-kPa (<20mWcm-2) on the proliferative capacity, colony-formation efficiency, genetic stability, and differentiation potential of hMSCs. Additionally, potential signaling pathways involved in LIUS-mediated proliferation of hMSCs are studied. Compared to non-stimulated controls, LIUS-treated hMSCs shows a 1.9-fold greater colony-forming efficiency and 2.5-fold higher rate of cell proliferation, respectively. Differential staining and qRT-PCR analysis for selective chondrogenic, osteogenic, and adipogenic markers further confirmed that the LIUS treatment did not impact the multipotency of hMSCs. LIUS-treated hMSCs expressed normal male karyotype. The synthesis of cyclin-D1, a master regulator of cellular proliferation, is upregulated under LIUS and its enhanced mRNA expression under LIUS is noted to be mediated by the activation of both MAPK/ERK and PI3K/AKT pathways. In conclusion, LIUS promotes proliferation and self-renewal capacity of hMSCs.

AB - Human mesenchymal stem cells (hMSCs) hold great potential for cellular based therapeutics and tissue engineering applications and their expansion is an interesting prospect due to their low availability from in vivo sources. Therefore, this study investigated the effect of continuous-wave low-intensity ultrasound (LIUS) at 5.0-MHz and 14.0-kPa (<20mWcm-2) on the proliferative capacity, colony-formation efficiency, genetic stability, and differentiation potential of hMSCs. Additionally, potential signaling pathways involved in LIUS-mediated proliferation of hMSCs are studied. Compared to non-stimulated controls, LIUS-treated hMSCs shows a 1.9-fold greater colony-forming efficiency and 2.5-fold higher rate of cell proliferation, respectively. Differential staining and qRT-PCR analysis for selective chondrogenic, osteogenic, and adipogenic markers further confirmed that the LIUS treatment did not impact the multipotency of hMSCs. LIUS-treated hMSCs expressed normal male karyotype. The synthesis of cyclin-D1, a master regulator of cellular proliferation, is upregulated under LIUS and its enhanced mRNA expression under LIUS is noted to be mediated by the activation of both MAPK/ERK and PI3K/AKT pathways. In conclusion, LIUS promotes proliferation and self-renewal capacity of hMSCs.

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