Decellularized Extracellular Matrix as a Potent Natural Biomaterial for Regenerative Medicine

Sadrabadi, Amin Ebrahimi; Baei, Payam; Hosseini, Samaneh; Eslaminejad, Mohamadreza Baghaban

doi:10.1007/5584_2020_504

Cited by 18 publications

(17 citation statements)

References 83 publications

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“…Furthermore, as the extracellular matrix (ECM) is important for normal cell growth and cell function, the use of decellularized material where the ECM stays intact seems a promising approach (Bryksin, Brown, Baksh, Finn, & Barker, 2014;Khan & Tanaka, 2017). As different cell types produce different types of ECM, the use of corneal fibroblast in this study provides an advantage over using for example skin fibroblasts to generate the cell sheets (Ebrahimi Sadrabadi, Baei, Hosseini, & Baghaban Eslaminejad, 2020). Using organ-matched cell types results in organ-specific ECM structures, which is important for biocompatibility.…”

Section: Discussionmentioning

confidence: 99%

Decellularized human corneal stromal cell sheet as a novel matrix for ocular surface reconstruction

Mertsch

Hasenzahl

Reichl

et al. 2020

J Tissue Eng Regen Med

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The shortage of donor corneas as well as the limitations of tissue substitutes leads to the necessity to develop alternative materials for ocular surface reconstruction. Corneal surface substitutes must fulfill specific requirements such as high transparency, low immunogenicity, and mechanical stability combined with elasticity. This in vitro study evaluates a decellularized matrix secreted from human corneal fibroblasts (HCF) as an alternative material for ocular surface reconstruction. HCF from human donors were cultivated with the supplementation of vitamin C to form a stable and thick matrix. Furthermore, due to enhanced cultivation time, a three‐dimensional like multilayered construct which partly mimics the complex structure of the corneal stroma could be generated. The formed human cell‐based matrices (so‐called cell sheets [CS]) were subsequently decellularized. The complete cell removal, collagen content, ultrastructure, and cell toxicity of the decellularized CS (DCS) as well as biomechanical properties were analyzed. Surgical feasibility was tested on enucleated porcine eyes. After decellularization and sterilization, a transparent, thick, cell free, and sterile tissue substitute resulted, which allowed expansion of limbal epithelial stem cells with no signs of cytotoxicity, and good surgical feasibility. DCS seem to be a promising new corneal tissue substitute derived from human cells without the limitation of donor material; however, future in vivo studies are necessary to further elucidate its potential for ocular surface reconstruction.

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Section: Discussionmentioning

confidence: 99%

Decellularized human corneal stromal cell sheet as a novel matrix for ocular surface reconstruction

Mertsch

Hasenzahl

Reichl

et al. 2020

J Tissue Eng Regen Med

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“…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%

“…One of the most promising approach to model ECM-based cell microenvironment is a decellularization of extracellular matrices provided bioactive and biocompatible materials consisting of a complex assembly of fibrillar proteins, matrix macromolecules and associated growth factors that often recapitulates the composition and organization of the original ECM microenvironments and creates the necessary microenvironment for the activity of cells in vitro or in vivo (Rana et al, 2017;Dzobo et al, 2019;Heath, 2019;Novoseletskaya et al, 2019;Ebrahimi Sadrabadi et al, 2020). To stimulate the production of ECM components MSCs can be cultured in 3D conditions such as cell multilayers, or cell sheets.…”

Section: Introductionmentioning

confidence: 99%

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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“…It is a vital and complex meshwork where structural and functional proteins, such as collagens (e.g., Collagen I), glycosaminoglycans (GAGs) (e.g., heparin and chondroitin sulfate), proteoglycans (e.g., decorin), and adhesion molecules (e.g., fibronectin), can be found. For any given tissue type, the ECM has an appropriate architectural design where there is a variation in the orientation, the nature, and the number of matrix components among the different tissues [ 24 , 25 , 26 ]. Tendons are mainly composed of ECM, where 68% corresponds to water, 30% to collagen, and 2% to elastin.…”

Section: Introductionmentioning

confidence: 99%

Decellularized Extracellular Matrix-Based Bioinks for Tendon Regeneration in Three-Dimensional Bioprinting

Khalak

García‐Villén

Ruiz‐Alonso

et al. 2022

IJMS

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In the last few years, attempts to improve the regeneration of damaged tendons have been rising due to the growing demand. However, current treatments to restore the original performance of the tissue focus on the usage of grafts; although, actual grafts are deficient because they often cannot provide enough support for tissue regeneration, leading to additional complications. The beneficial effect of combining 3D bioprinting and dECM as a novel bioink biomaterial has recently been described. Tendon dECMs have been obtained by using either chemical, biological, or/and physical treatments. Although decellularization protocols are not yet standardized, recently, different protocols have been published. New therapeutic approaches embrace the use of dECM in bioinks for 3D bioprinting, as it has shown promising results in mimicking the composition and the structure of the tissue. However, major obstacles include the poor structural integrity and slow gelation properties of dECM bioinks. Moreover, printing parameters such as speed and temperature have to be optimized for each dECM bioink. Here, we show that dECM bioink for 3D bioprinting provides a promising approach for tendon regeneration for future clinical applications.

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Decellularized Extracellular Matrix as a Potent Natural Biomaterial for Regenerative Medicine

Cited by 18 publications

References 83 publications

Decellularized human corneal stromal cell sheet as a novel matrix for ocular surface reconstruction

Decellularized human corneal stromal cell sheet as a novel matrix for ocular surface reconstruction

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

Decellularized Extracellular Matrix-Based Bioinks for Tendon Regeneration in Three-Dimensional Bioprinting

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