Uniaxial Cyclic Tensile Stretching at 8% Strain Exclusively Promotes Tenogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells

Nam, Hui Yin; Murphy, Belinda; Abbas, Azlina Amir; Merican, Azhar M.; Kamarul, Tunku

doi:10.1155/2019/9723025

Cited by 31 publications

(44 citation statements)

References 67 publications

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“…The organization of the F-actin in the cells loaded in vitro was unchanged compared to the non-loaded control, with no major direction. Various studies have proven that different cell types are capable of sensing mechanical loading and align the cytoskeleton in the direction of uniaxial strain [36][37][38][39]. In the present study, the applied strain was equibiaxial, and theoretically comes from all directions.…”

Section: Discussionmentioning

confidence: 73%

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

Fleischhacker

Klatte‐Schulz

Minkwitz

et al. 2020

IJMS

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Mechanical force is a key factor for the maintenance, adaptation, and function of tendons. Investigating the impact of mechanical loading in tenocytes and tendons might provide important information on in vivo tendon mechanobiology. Therefore, the study aimed at understanding if an in vitro loading set up of tenocytes leads to similar regulations of cell shape and gene expression, as loading of the Achilles tendon in an in vivo mouse model. In vivo: The left tibiae of mice (n = 12) were subject to axial cyclic compressive loading for 3 weeks, and the Achilles tendons were harvested. The right tibiae served as the internal non-loaded control. In vitro: tenocytes were isolated from mice Achilles tendons and were loaded for 4 h or 5 days (n = 6 per group) based on the in vivo protocol. Histology showed significant differences in the cell shape between in vivo and in vitro loading. On the molecular level, quantitative real-time PCR revealed significant differences in the gene expression of collagen type I and III and of the matrix metalloproteinases (MMP). Tendon-associated markers showed a similar expression profile. This study showed that the gene expression of tendon markers was similar, whereas significant changes in the expression of extracellular matrix (ECM) related genes were detected between in vivo and in vitro loading. This first pilot study is important for understanding to which extent in vitro stimulation set-ups of tenocytes can mimic in vivo characteristics.

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Section: Discussionmentioning

confidence: 73%

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

Fleischhacker

Klatte‐Schulz

Minkwitz

et al. 2020

IJMS

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“…Moreover, also the percentage of strain applied can have different effects on tenogenic differentiation. For instance, tenocytes cultured for 12 days upon poly(glycerol-sebacate) (PGS) sheets under 6% cyclic strain exhibited a tendon-like gene expression profile compared to 3% and 0% strain groups [286], while uniaxial cyclic tensile stretching at 8% strain exclusively induced tenogenic differentiation of human bone marrow-derived mesenchymal stem cells, with protein and gene expression comparable to primary tenocytes [287]. On the other hand, constant strain has been found to negatively affect tendon diameter [288], also inhibiting cell proliferation and increasing apoptosis, potentially through the increase of heat shock protein (HSP)-72 expression [289].…”

Section: Physical Stimulimentioning

confidence: 99%

In Vitro Innovation of Tendon Tissue Engineering Strategies

Citeroni

Ciardulli

Russo

et al. 2020

IJMS

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Tendinopathy is the term used to refer to tendon disorders. Spontaneous adult tendon healing results in scar tissue formation and fibrosis with suboptimal biomechanical properties, often resulting in poor and painful mobility. The biomechanical properties of the tissue are negatively affected. Adult tendons have a limited natural healing capacity, and often respond poorly to current treatments that frequently are focused on exercise, drug delivery, and surgical procedures. Therefore, it is of great importance to identify key molecular and cellular processes involved in the progression of tendinopathies to develop effective therapeutic strategies and drive the tissue toward regeneration. To treat tendon diseases and support tendon regeneration, cell-based therapy as well as tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated. This review aims to compare different available tendon in vitro differentiation strategies to clarify the state of art regarding the differentiation process.

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“…Our previous study shows that mechanical stimulation can trigger tenogenic differentiation of hMSCs [26]. From 6 hours to 72 hours, the expression of tenogenic markers appeared to be upregulated, with the exception of scleraxis, which was present at a higher level at 24 hours but decreased at later time points (see Figure 5(a)).…”

Section: Influence Of Enac Inhibition On Tenogenic Differentiationmentioning

confidence: 76%

“…The mRNA expression of tenogenic lineages and ENaC subunits (see Table 1 ) was quantified by the QuantiGene 2.0 Plex assay (2.0 plex set 12082, Panomics/Affymetrix Inc., Fremont, CA, USA). The housekeeping gene was PGK1 (phosphoglycerate kinase 1), which has been observed in our previous pilot study [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…In order to obtain a sufficient number of hMSCs, the cells were serially passaged and expanded up to passage-2 (see Figures 1(c)-1(e)) before being used for experiment use. The hMSCs used in our study were well-characterized by flow cytometric analysis and induction of multilineage differentiation assay, according to the previous protocols used in our laboratory [25,26].…”

Section: Harvesting Bone Marrow Specimens From Humanmentioning

confidence: 99%

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Mechanical Strain-Mediated Tenogenic Differentiation of Mesenchymal Stromal Cells Is Regulated through Epithelial Sodium Channels

Nam

Murali

Ahmad

et al. 2020

Stem Cells International

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It has been suggested that mechanical strain may elicit cell differentiation in adult somatic cells through activation of epithelial sodium channels (ENaC). However, such phenomenon has not been previously demonstrated in mesenchymal stromal cells (MSCs). The present study was thus conducted to investigate the role of ENaC in human bone marrow-derived MSCs (hMSCs) tenogenic differentiation during uniaxial tensile loading. Passaged-2 hMSCs were seeded onto silicone chambers coated with collagen I and subjected to stretching at 1 Hz frequency and 8% strain for 6, 24, 48, and 72 hours. Analyses at these time points included cell morphology and alignment observation, immunocytochemistry and immunofluorescence staining (collagen I, collagen III, fibronectin, and N-cadherin), and gene expression (ENaC subunits, and tenogenic markers). Unstrained cells at similar time points served as the control group. To demonstrate the involvement of ENaC in the differentiation process, an ENaC blocker (benzamil) was used and the results were compared to the noninhibited hMSCs. ENaC subunits’ (α, β, γ, and δ) expression was observed in hMSCs, although only α subunit was significantly increased during stretching. An increase in tenogenic genes’ (collagen1, collagen3, decorin, tenascin-c, scleraxis, and tenomodulin) and proteins’ (collagen I, collagen III, fibronectin, and N-cadherin) expression suggests that hMSCs underwent tenogenic differentiation when subjected to uniaxial loading. Inhibition of ENaC function resulted in decreased expression of these markers, thereby suggesting that ENaC plays a vital role in tenogenic differentiation of hMSCs during mechanical loading.

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Uniaxial Cyclic Tensile Stretching at 8% Strain Exclusively Promotes Tenogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells

Cited by 31 publications

References 67 publications

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

In Vitro Innovation of Tendon Tissue Engineering Strategies

Mechanical Strain-Mediated Tenogenic Differentiation of Mesenchymal Stromal Cells Is Regulated through Epithelial Sodium Channels

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