Differentiation Potential of Mesenchymal Stem Cells Is Related to Their Intrinsic Mechanical Properties

Han, Ihn; Kwon, Byungsu; Park, Hun-Kuk; Kim, Kyung Sook

doi:10.5213/inj.1734856.428

Cited by 50 publications

(44 citation statements)

References 27 publications

(32 reference statements)

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“…[16] On stiffer materials and with more cellular tension human mesenchymal stromal cells (hMSCs) show increased osteogenic differentiation, while softer materials and lower cellular tension enhance differentiation to chondro-and adipogenic lineages. [17][18][19][20][21] These changes in hMSC differentiation have been shown to be orchestrated by actin stress fibers [22] , focal adhesions [22] , lamin A and C [23] and Yes-associated protein 1 (YAP1). [24,25] While other material properties are relatively well studied, the dimensionality (2D v. 3D) of a material has not yet been widely studied.…”

Section: Introductionmentioning

confidence: 99%

Dimensionality changes actin network through lamin A and C and zyxin

Zonderland

Moldero

Mota

et al. 2019

Preprint

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The actin cytoskeleton plays a key role in differentiation of human mesenchymal stromal cells (hMSCs), but its regulation in 3D tissue engineered scaffolds remains poorly studied. hMSCs cultured on 3D electrospun scaffolds made of a stiff material do not form actin stress fibers, contrary to hMSCs on 2D films of the same material. On 3D electrospun-and 3D additive manufactured scaffolds, hMSCs also displayed fewer focal adhesions, lower lamin A and C expression and less YAP1 nuclear localization. Together, this shows that dimensionality prevents the build-up of cellular tension, even on stiff materials. Knock down of either lamin A and C or zyxin resulted in fewer stress fibers in the cell center. Zyxin knock down reduced lamin A and C expression, but not vice versa, showing that this signal chain starts from the outside of the cell. Our study demonstrates that dimensionality changes the actin cytoskeleton through lamin A and C and zyxin, an important insight for future scaffold design, as the actin network, focal adhesions and nuclear stiffness are all critical for hMSC differentiation.

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Section: Introductionmentioning

confidence: 99%

Dimensionality changes actin network through lamin A and C and zyxin

Zonderland

Moldero

Mota

et al. 2019

Preprint

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“…Secondly, the ability of MSCs to differentiate is well recognized, which makes them an excellent resource to produce different cellular lineages, and are a medium widely used to replace dead or lost cells in cases of neurodegeneration (Bai et al, ; Han, Kwon, Park, & Kim, ). Several authors have reported on the capacity of MSCs to differentiate into neuron‐like cells, indicated through display of neuronal morphological features and expression of brain cell markers, such as β‐tubulin III (Tuj‐1), nestin, NeuN, and glial fibrillary acidic protein (Wang et al, ; Ying, Hu, & Cheng, ).…”

Section: Discussionmentioning

confidence: 99%

Physical exercise and human adipose‐derived mesenchymal stem cells ameliorate motor disturbances in a male rat model of Parkinson's disease

Cucarián

Berrío

Rodrigues

et al. 2019

J of Neuroscience Research

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Parkinson's disease (PD) is a disabling and highly costly neurodegenerative condition with worldwide prevalence. Despite advances in treatments that slow progression and minimize locomotor impairments, its clinical management is still a challenge. Previous preclinical studies, using mesenchymal stem cell (MSC) transplantation and isolated physical exercise (EX), reported beneficial results for treatment of PD. Therefore, this experimental randomized study aimed to elucidate the therapeutic potential of combined therapy using adipose-derived human MSCs (ADSCs) grafted into the striatum in conjunction with aerobic treadmill training, specifically in terms of locomotor performance in a unilateral PD rat model induced by 6-hydroxydopamine (6-OHDA). Forty-one male Wistar rats were categorized into five groups in accordance with the type of treatment to which they were subjected (Sham, 6-OHDA − injury, 6-OHDA + exercise, 6-OHDA + cells, and 6-OHDA + combined). Subsequently, dopaminergic depletion was assessed by the methylphenidate challenge and the specified therapeutic intervention was conducted in each group. The foot fault task was performed at the end of the experiment to serve as an assessment of motor skills. The results showed that despite disturbances in motor balance and coordination, locomotor dysfunction was ameliorated in all treatment categories in comparison to the injury group (sign test, p < 0.001, effect size: 0.71). The exercise alone and combined groups were the categories that exhibited the best recovery in terms of movement performance (p < 0.001). Overall, this study confirms that exercise is a powerful option to improve motor function and a promising adjuvant intervention for stem cell transplantation in the treatment of PD motor symptoms.

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“…One important property of bone marrow-derived mesenchymal stem cells is to differentiate into different specialized cell types such as osteoblasts and adipocytes. 28,29 Along with the capability to produce growth factors, mesenchymal stem cells need their capability of differentiating into different cell types to boost regeneration of injured tissues, 30 and hence exert their therapeutic role. In order to determine whether labeling our mesenchymal stem cells with IO-MI NPs will affect their differentiation capabilities, we performed osteogenic and adipogenic differentiation experiments for labeled and nonlabeled FGF21 MSCs ( Figure 4A) and mCherry MSCs ( Figure 4B).…”

Section: Influence Of Labeling the Mesenchymal Stem Cells With Nanopamentioning

confidence: 99%

<p>Efficient Labeling Of Mesenchymal Stem Cells For High Sensitivity Long-Term MRI Monitoring In Live Mice Brains</p>

Ali¹,

Shahror²,

Chen³

2020

IJN

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Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/R_ECxLGJvxw Background: Regenerative medicine field is still lagging due to the lack of adequate knowledge regarding the homing of therapeutic cells towards disease sites, tracking of cells during treatment, and monitoring the biodistribution and fate of cells. Such necessities require labeling of cells with imaging agents that do not alter their biological characteristics, and development of suitable non-invasive imaging modalities. Purpose: We aimed to develop, characterize, and standardize a facile labeling strategy for engineered mesenchymal stem cells without altering their viability, secretion of FGF21 protein (neuroprotective), and differentiation capabilities for non-invasive longitudinal MRI monitoring in live mice brains with high sensitivity. Methods: We compared the labeling efficiency of different commercial iron oxide nanoparticles towards our stem cells and determined the optimum labeling conditions using prussian blue staining, confocal microscopy, transmission electron microscopy, and flow cytometry. To investigate any change in biological characteristics of labeled cells, we tested their viability by WST-1 assay, expression of FGF21 by Western blot, and adipogenic and osteogenic differentiation capabilities. MRI contrast-enhancing properties of labeled cells were investigated in vitro using cell-agarose phantoms and in mice brains transplanted with the therapeutic stem cells. Results: We determined the nanoparticles that showed best labeling efficiency and least extracellular aggregation. We further optimized their labeling conditions (nanoparticles concentration and media supplementation) to achieve high cellular uptake and minimal extracellular aggregation of nanoparticles. Cell viability, expression of FGF21 protein, and differentiation capabilities were not impeded by nanoparticles labeling. Low number of labeled cells produced strong MRI signal decay in phantoms and in live mice brains which were visible for 4 weeks post transplantation. Conclusion: We established a standardized magnetic nanoparticle labeling platform for stem cells that were monitored longitudinally with high sensitivity in mice brains using MRI for regenerative medicine applications.

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Differentiation Potential of Mesenchymal Stem Cells Is Related to Their Intrinsic Mechanical Properties

Cited by 50 publications

References 27 publications

Dimensionality changes actin network through lamin A and C and zyxin

Dimensionality changes actin network through lamin A and C and zyxin

Physical exercise and human adipose‐derived mesenchymal stem cells ameliorate motor disturbances in a male rat model of Parkinson's disease

<p>Efficient Labeling Of Mesenchymal Stem Cells For High Sensitivity Long-Term MRI Monitoring In Live Mice Brains</p>

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