Aging-related viscoelasticity variation of tendon stem cells (TSCs) characterized by quartz thickness shear mode (TSM) resonators

Abstract

Aging not only affects the whole body performance but also alters cellular biological properties, including cell proliferation and differentiation. This study was designed to determine the effect of aging on the mechanical properties of tendon stem cells (TSCs), a newly discovered stem cell type in tendons, using quartz thickness shear mode (TSM) resonators. TSCs were isolated from both old and young rats, and allowed to grow to confluency on the surface of TSM resonators. The admittance spectrums of TSM with TSC monolayer were acquired, and a series of complex shear modulus G′ + jG″ as well as average thickness hTSC were calculated based on a two-layer-loading transmission line model (TLM) for TSM resonator sensor. The results showed an overall increase in G′, G″ and hTSC during aging process. Specifically, the storage modulus G′ of aging TSCs was over ten times than that of young, revealing an important increase in stiffness of aging TSCs. Additionally, through phase-contrast and scanning electronic microscopy, it was shown that aging TSCs were large, flat and heterogeneous in morphologies while young TSCs were uniformly elongated. Increased cell size and irregular cell shape might be associated with the dense cytoskeleton organization, which could lead to an increase in both stiffness and viscosity. These results are in agreement with previously published data using different measurement methods, indicating TSM resonator sensor as a promising tool to measure the mechanical properties of cells.

Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats

“…Aging is known to decrease the functional competence of the body. In tendons, aging causes a number of changes; it increases tendon stiffness, changes TSC morphology from elongated and uniform in young tendons to large, flat and heterogeneous in aging tendons [ 29 ], decreases TSC proliferation, down-regulates the expression of stem cell markers (OCT-4, nucleostemin, Sca-1 and SSEA-1), and tenocyte related markers (Collagen I and tenomodulin) [ 24 ], reduces collagen synthesis and turnover [ 30 , 31 ], increases the senescent marker, CCN-1 [ 32 ], and causes other related changes. Emerging evidence suggests that these aging related changes can be reversed by the effects of moderate exercise such as MTR on TSCs [ 6 , 22 , 24 ], which play a critical role in tendon maintenance and repair.…”

“…Recently, using thickness shear mode (TSM) resonators we showed that aging rat tendon cells exhibit increased stiffness, along with extensively changed TSC morphology (large, flat and heterogeneous) when compared to young TSCs (elongated and uniform) [ 29 ]. This indicates that the altered TSC morphology and the likely molecular changes that concurrently occur may contribute to the increased stiffness in aging tendons.…”

Tendon stem/progenitor cell ageing: Modulation and rejuvenation

“…In addition, aged TSPCs are obviously larger in size, have more podia, spread further, and exhibit more robust actin stress fibers and a higher actin content that distorts the balance of the actin cytoskeleton organization[14,55,56], which has also been confirmed by analyses of microarray data in aged TSPCs[14]. Additionally, aged TSPCs display a large, flat and heterogeneous morphology, while younger cells exhibit the morphology of uniform elongated[57]. An increase in the size is often associated with cell senescence[50,55,56].…”

“…One study revealed an overall increase in G′, G″ and H TSPC with ageing, which are valuable indicators of the cellular viscoelasticity that correspond to the storage modulus (G’), loss modulus (G’’) and average thickness (H TSPC ), respectively. A dense cytoskeletal organization might result in a larger cell size and anomalous cell shape and is the cause of the increase in stiffness and viscosity[57]. Other authors had also detected an increase in the cell stiffness and size of A-TSPCs, as well as a denser and well-structured actin cytoskeleton.…”

XIST lost induces ovarian cancer stem cells to acquire taxol resistance via a KMT2C-dependent way

“…Tumor stem cells (TCCs) are abnormal tissues formed by the proliferation of tumor-forming TCCs. TCCs are closely related to the malignant biological behavior of tumors, and are the determinants of tumorigenesis, development, invasion, metastasis, and drug resistance [6]. The theory of cancer stem cells proposes a new elaboration for the origin of tumors, pointing out new targets for the treatment of tumors.…”