Three-Dimensional Culture Reduces Cell Size By Increasing Vesicle Excretion

Mo, Miaohua; Zhou, Ying; Li, Sen; Wu, Yaojiong

doi:10.1002/stem.2729

Cited by 30 publications

(19 citation statements)

References 31 publications

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“…After 3D spheroids culture, the diameter of MSCs significantly decreased (Fig. 1 A–D), which is consistent with our previous studies [ 11 , 14 , 27 ]. Importantly, annexin V/PI staining of the cells by flow cytometry analysis showed that the 3D spheroid culture did not increase cell apoptosis (Fig.…”

Section: Resultssupporting

confidence: 92%

Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia

Dong

et al. 2021

Stem Cell Res Ther

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Background We show previously that three-dimensional (3D) spheroid cultured mesenchymal stem cells (MSCs) exhibit reduced cell size thus devoid of lung entrapment following intravenous (IV) infusion. In this study, we determined the therapeutic effect of 3D-cultured MSCs on ischemic stroke and investigated the mechanisms involved. Methods Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion. 1 × 106 of 3D- or 2D-cultured MSCs, which were pre-labeled with GFP, were injected through the tail vain three and seven days after MCAO. Two days after infusion, MSC engraftment into the ischemic brain tissues was assessed by histological analysis for GFP-expressing cells, and infarct volume was determined by MRI. Microglia in the lesion were sorted and subjected to gene expressional analysis by RNA-seq. Results We found that infusion of 3D-cultured MSCs significantly reduced the infarct volume of the brain with increased engraftment of the cells into the ischemic tissue, compared to 2D-cultured MSCs. Accordingly, in the brain lesion of 3D MSC-treated animals, there were significantly reduced numbers of amoeboid microglia and decreased levels of proinflammatory cytokines, indicating attenuated activation of the microglia. RNA-seq of microglia derived from the lesions suggested that 3D-cultured MSCs decreased the response of microglia to the ischemic insult. Interestingly, we observed a decreased expression of mincle, a damage-associated molecular patterns (DAMPs) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke. Conclusions Our data indicate that 3D-cultured MSCs exhibit enhanced repair to ischemic stroke, probably through a suppression to ischemia-induced microglial activation.

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Section: Resultssupporting

confidence: 92%

Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia

Dong

et al. 2021

Stem Cell Res Ther

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“…50 Also, 3D cultures show an increase in vesicle secretion, which could potentially contain STC1. 46 These results are in line with ours and hinted at a mechanosensitive regulation of STC1. Here, we have shown that STC1 is indeed regulated through mechanotransduction pathways, specifically through zyxin and actin-myosin.…”

Section: Discussionsupporting

confidence: 91%

“…Others have reported that depolymerization of actin results in increased vesicle secretion, hinting at a potential mechanism of the increased STC1 secretion. 46 The number of zyxin positive focal adhesions was also reduced in the hypotonic and nutrient deprivation conditions, but not the hypertonic condition, correlating with the STC1 secretion. When zyxin was knocked down, we also found an increase in STC1 secretion, proving a causal link between the two.…”

Section: Discussionmentioning

confidence: 92%

Mechanosensitive regulation of stanniocalcin-1 by zyxin and actin-myosin in human mesenchymal stromal cells

et al. 2020

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Stanniocalcin-1 (STC1) secreted by mesenchymal stromal cells (MSCs) has antiinflammatory functions, reduces apoptosis, and aids in angiogenesis, both in vitro and in vivo. However, little is known about the molecular mechanisms of its regulation. Here, we show that STC1 secretion is increased only under specific cell-stress conditions. We find that this is due to a change in actin stress fibers and actin-myosin tension. Abolishment of stress fibers by blebbistatin and knockdown of the focal adhesion protein zyxin leads to an increase in STC1 secretion. To also study this connection in 3D, where few focal adhesions and actin stress fibers are present, STC1 expression was analyzed in 3D alginate hydrogels and 3D electrospun scaffolds. Indeed, STC1 secretion was increased in these low cellular tension 3D environments. Together, our data show that STC1 does not directly respond to cell stress, but that it is regulated through mechanotransduction. This research takes a step forward in the fundamental understanding of STC1 regulation and can have implications for cell-based regenerative medicine, where cell survival, anti-inflammatory factors, and angiogenesis are critical.

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“…Wang et al demonstrated that with the successive adherent cultures of MSCs, the expression level of integrins increased, which was associated with higher levels of phospho-focal adhesion kinase (FAK) and increased attachment to endothelial cells [ 73 ]. Interestingly, MSCs cultured as 3D spheroids are characterized by a significantly smaller size and did not cause detectable infarct in the brain, as demonstrated by Ge et al [ 71 ], and the most plausible reason is that a short period of 3D spheroid culture of MSCs was enough to reduce the size of these cells [ 74 ] as well as the expression levels of many integrins [ 73 ]. Our analysis of the literature shows that MSCs at passages 3 and 4 were most frequently used in clinical trials.…”

Section: Resultsmentioning

confidence: 99%

Influence of Hypothermic Storage Fluids on Mesenchymal Stem Cell Stability: A Comprehensive Review and Personal Experience

Ścieżyńska

Soszyńska

Szpak

et al. 2021

Cells

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Mesenchymal stem cells have generated a great deal of interest due to their potential use in regenerative medicine and tissue engineering. Examples illustrating their therapeutic value across various in vivo models are demonstrated in the literature. However, some clinical trials have not proved their therapeutic efficacy, showing that translation into clinical practice is considerably more difficult and discrepancies in clinical protocols can be a source of failure. Among the critical factors which play an important role in MSCs’ therapeutic efficiency are the method of preservation of the stem cell viability and various characteristics during their storage and transportation from the GMP production facility to the patient’s bedside. The cell storage medium should be considered a key factor stabilizing the environment and greatly influencing cell viability and potency and therefore the effectiveness of advanced therapy medicinal product (ATMP) based on MSCs. In this review, we summarize data from 826 publications concerning the effect of the most frequently used cell preservation solutions on MSC potential as cell-based therapeutic medicinal products.

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Three-Dimensional Culture Reduces Cell Size By Increasing Vesicle Excretion

Cited by 30 publications

References 31 publications

Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia

Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia

Mechanosensitive regulation of stanniocalcin-1 by zyxin and actin-myosin in human mesenchymal stromal cells

Influence of Hypothermic Storage Fluids on Mesenchymal Stem Cell Stability: A Comprehensive Review and Personal Experience

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