Engineering Stem Cell-Derived Extracellular Matrices: Decellularization, Characterization, and Biological Function

Sart, Sébastien; Jeske, Richard; Chen, Xingchi; Ma, Teng; Li, Yan

doi:10.1089/ten.teb.2019.0349

Cited by 46 publications

(58 citation statements)

References 194 publications

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“…shown that MSCs cultured on these surfaces exhibited improved proliferation capacity, maintenance of phenotype, and increased differentiation potential (Shakouri-Motlagh et al, 2017;Sart et al, 2020). However, the mechanisms of these effects remained to be poor understood.…”

Section: Discussionmentioning

confidence: 99%

“…The development and application of dECM matrices, prepared both by decellularization of tissues or whole organs and cell-based constructs, has grown rapidly in the fields of cell biology, tissue engineering and regenerative medicine in recent years ( Hoshiba, 2017 ; Rana et al, 2017 ; Shakouri-Motlagh et al, 2017 ; Parmaksiz et al, 2020 ; Riis et al, 2020 ; Sart et al, 2020 ). The source of cells producing ECM is of great importance for realizing its functional role ( Cramer and Badylak, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…MSC-produced dECM has recently emerged as a promising substrate for the improved expansion of different cells ( Chen et al, 2007 ; Lai et al, 2010 ; Ng et al, 2014 ; Wu et al, 2016 ). It was shown that MSCs cultured on these surfaces exhibited improved proliferation capacity, maintenance of phenotype, and increased differentiation potential ( Shakouri-Motlagh et al, 2017 ; Sart et al, 2020 ). However, the mechanisms of these effects remained to be poor understood.…”

Section: Discussionmentioning

confidence: 99%

“…Based on our previous results and literature data the following detergents for decellularization were selected: zwitter-ion detergent -CHAPS and ion detergent -sodium deoxycholate. Ionic detergents, such as sodium deoxycholate, are actively use for the decellularization of organs and tissues (Rana et al, 2017;Dzobo et al, 2019;Heath, 2019;Ebrahimi Sadrabadi et al, 2020;Sart et al, 2020). On the other side, this type of detergents can contribute the leaching of a significant part of the ECM from the cell sheet.…”

Section: Preparation Of Msc-produced Decmmentioning

confidence: 99%

“…To stimulate the production of ECM components MSCs can be cultured in 3D conditions such as cell multilayers, or cell sheets. Decellularization of cell sheets provides the preparation of ECM with a composition of protein components close to the native structure and composition (Cheng et al, 2014;Sart et al, 2020). Different decellularizing agents might be used including detergents, enzymes, apoptosis inductors, etc., and an effective combination should be adjusted based on required conservation of ECM structure and effectiveness of DNA removal (Gilpin and Yang, 2017;Hoshiba, 2017;Shakouri-Motlagh et al, 2017;Cramer and Badylak, 2019;Heath, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Novoseletskaya

Grigorieva

Nimiritsky

et al. 2020

Front. Cell Dev. Biol.

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Extracellular matrix (ECM) provides both structural support and dynamic microenvironment for cells regulating their behavior and fate. As a critical component of stem cell niche ECM maintains stem cells and activates their proliferation and differentiation under specific stimuli. Mesenchymal stem/stromal cells (MSCs) regulate tissue-specific stem cell functions locating in their immediate microenvironment and producing various bioactive factors, including ECM components. We evaluated the ability of MSC-produced ECM to restore stem and progenitor cell microenvironment in vitro and analyzed the possible mechanisms of its effects. Human MSC cell sheets were decellularized by different agents (detergents, enzymes, and apoptosis inductors) to select the optimized combination (CHAPS and DNAse I) based on the conservation of decellularized ECM (dECM) structure and effectiveness of DNA removal. Prepared dECM was non-immunogenic, supported MSC proliferation and formation of larger colonies in colony-forming unit-assay. Decellularized ECM effectively promoted MSC trilineage differentiation (adipogenic, osteogenic, and chondrogenic) compared to plastic or plastic covered by selected ECM components (collagen, fibronectin, laminin). Interestingly, dECM produced by human fibroblasts could not enhance MSC differentiation like MSC-produced dECM, indicating cell-specific functionality of dECM. We demonstrated the significant integrin contribution in dECM-cell interaction by blocking the stimulatory effects of dECM with RGD peptide and suggested the involvement of key intracellular signaling pathways activation (pERK/ERK and pFAK/FAK axes, pYAP/YAP and beta-catenin) in the observed processes based on the results of inhibitory analysis. Taken together, we suppose that MSC-produced dECM may mimic stem cell niche components in vitro and maintain multipotent progenitor cells to insure their effective response to external differentiating stimuli upon activation. The obtained data provide more insights into the possible role of MSC-produced ECM in stem and progenitor cell regulation within their niches. Our results are also useful for the developing of dECM-based cell-free products for regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Msc-produced Decmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Novoseletskaya

Grigorieva

Nimiritsky

et al. 2020

Front. Cell Dev. Biol.

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Emerging Strategies for Optimizing Cell‐Derived Decellularized Extracellular Matrix Scaffolds in Tissue Engineering

Chen,

Zhang,

2024

Adv Eng Mater

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As an ideal biological scaffold, cell‐derived decellularized extracellular matrix (dECM) is attracting increasing attention and has been prepared and studied for tissue engineering. However, a few barriers prevent its extensive clinical usage, indicating that it requires further optimization. This review starts with a brief introduction to the benefits and limitations of dECM as a biomaterial. Then, it provides a novel perspective summarizing and describing methods for dECM optimization, delineating strategies to optimize regular cell‐derived dECM sheet preparation and additional biochemical or mechanophysical procedures to further modify the scaffold. These innovative approaches equip engineered biomaterials based on cell‐derived dECMs with key properties and functionalities, thus providing a great opportunity for their broader future therapeutic applications. Finally, several ideas and directions for future development are also prospected.This article is protected by copyright. All rights reserved.

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Engineering Extracellular Matrix‐Bound Nanovesicles Secreted by Three‐Dimensional Human Mesenchymal Stem Cells

Liu

Chen

Liu

et al. 2023

Adv Healthcare Materials

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Extracellular matrix (ECM) in the human tissue contains vesicles, which are defined as matrix‐bound nanovesicles (MBVs). MBVs serve as one of the functional components in ECM, recapitulating part of the regulatory roles and in vivo microenvironment. In this study, extracellular vesicles from culture supernatants (SuEVs) and MBVs are isolated from the conditioned medium or ECM, respectively, of 3D human mesenchymal stem cells. Nanoparticle tracking analysis shows that MBVs are smaller than SuEVs (100–150 nm). Transmission electron microscopy captures the typical cup shape morphology for both SuEVs and MBVs. Western blot reveals that MBVs have low detection of some SuEV markers such as syntenin‐1. miRNA analysis of MBVs shows that 3D microenvironment enhances the expression of miRNAs such as miR‐19a and miR‐21. In vitro functional analysis shows that MBVs can facilitate human pluripotent stem cell‐derived forebrain organoid recovery after starvation and promote high passage fibroblast proliferation. In macrophage polarization, 2D MBVs tend to suppress the pro‐inflammatory cytokine IL‐12β, while 3D MBVs tend to enhance the anti‐inflammatory cytokine IL‐10. This study has the significance in advancing the understanding of the bio‐interface of nanovesicles with human tissue and the design of cell‐free therapy for treating neurological disorders such as ischemic stroke.

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Engineering Stem Cell-Derived Extracellular Matrices: Decellularization, Characterization, and Biological Function

Cited by 46 publications

References 194 publications

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Emerging Strategies for Optimizing Cell‐Derived Decellularized Extracellular Matrix Scaffolds in Tissue Engineering

Engineering Extracellular Matrix‐Bound Nanovesicles Secreted by Three‐Dimensional Human Mesenchymal Stem Cells

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