Low Intensity Vibrations Augment Mesenchymal Stem Cell Proliferation and Differentiation Capacity During in vitro Expansion

Authors

Guniz Bas, Boise State University
Stacie Loisate, Boise State University
Stephanie F. Hudon, Boise State UniversityFollow
Kali Woods, Boise State UniversityFollow
Eric J. Hayden, Boise State UniversityFollow
Xinzhu Pu, Boise State UniversityFollow
Richard Beard, Boise State UniversityFollow
Julia T. Oxford, Boise State UniversityFollow
Gunes Uzer, Boise State UniversityFollow

Document Type

Article

Publication Date

6-10-2020

Abstract

A primary component of exercise, mechanical signals, when applied in the form of low intensity vibration (LIV), increases mesenchymal stem cell (MSC) osteogenesis and proliferation. While it is generally accepted that exercise effectively combats the deleterious effects of aging in the musculoskeletal system, how long-term exercise affects stem cell aging, which is typified by reduced proliferative and differentiative capacity, is not well explored. As a first step in understanding the effect of long-term application of mechanical signals on stem cell function, we investigated the effect of LIV during in vitro expansion of MSCs. Primary MSCs were subjected to either a control or to a twice-daily LIV regimen for up to sixty cell passages (P60) under in vitro cell expansion conditions. LIV effects were assessed at both early passage (EP) and late passage (LP). At the end of the experiment, P60 cultures exposed to LIV maintained a 28% increase of cell doubling and a 39% reduction in senescence-associated β-galactosidase activity (p < 0.01) but no changes in telomere lengths and p16^INK4a levels were observed. Prolonged culture-associated decreases in osteogenic and adipogenic capacity were partially protected by LIV in both EP and LP groups (p < 0.05). Mass spectroscopy of late passage MSC indicated a synergistic decrease of actin and microtubule cytoskeleton-associated proteins in both control and LIV groups while LIV induced a recovery of proteins associated with oxidative reductase activity. In summary, our findings show that the application of long-term mechanical challenge (+LIV) during in vitro expansion of MSCs for sixty passages significantly alters MSC proliferation, differentiation and structure. This suggests LIV as a potential tool to investigate the role of physical activity during aging.

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Publication Information

Bas, Guniz; Loisate, Stacie; Hudon, Stephanie F.; Woods, Kali; Hayden, Eric J.; Pu, Xinzhu; Beard, Richard; Oxford, Julia T.; and Uzer, Gunes. (2020). "Low Intensity Vibrations Augment Mesenchymal Stem Cell Proliferation and Differentiation Capacity During in vitro Expansion". Scientific Reports, 10, 9369. https://doi.org/10.1038/s41598-020-66055-0