Soft extracellular matrix enhances inflammatory activation of mesenchymal stromal cells to induce monocyte production and trafficking

Wong, Sing Wan; Lenzini, Stephen; Cooper, Madeline; Mooney, David J.; Shin, Jae‐Won

doi:10.1126/sciadv.aaw0158

Cited by 92 publications

(61 citation statements)

References 62 publications

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“…Encapsulating MSC in injectable hydrogels is extensively explored to increase retention time and to modulate the cellular activity in situ ( Farhat et al, 2019 ; Wong et al, 2020 ) by providing the cells with a 3D microenvironment that protects and promotes an anti-inflammatory and regenerative response, see outline in Figure 1 . Techniques range from single cell encapsulation to larger scaffolds with macroporous structure ( Kim et al, 2019 ).…”

Section: Modulating the 3d Environment For Treatmentmentioning

confidence: 99%

“…Bone marrow-derived MSC were encapsulated in alginate-based hydrogels with different stiffnesses and pre-cultured prior to exposure to the inflammatory cytokine TNF-α. MSC preconditioned in the softer hydrogel in combination with TNFα had an improved effect in controlling monocyte turnover ( Wong et al, 2020 ). These studies demonstrate how intrinsic cues of the microenvironment impact cellular behavior that can be harnessed in improving the therapeutic potential of MSCs.…”

Section: Modulating the 3d Environment For Treatmentmentioning

confidence: 99%

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Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

et al. 2021

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It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal stromal/stem cells (MSC) have been shown to have immunomodulatory properties and may be potent actors regulating tissue remodelling and regenerative cell responses upon lung injury. Using MSC in cell-based therapy holds promise for treatment of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, so far clinical trials with MSCs in COPD have not had a significant impact on disease amelioration nor on IPF, where low cell survival rate and pulmonary retention time are major hurdles to overcome. Research shows that the microenvironment has a profound impact on transplanted MSCs. In our studies on acellular lung tissue slices (lung scaffolds) from IPF patients versus healthy individuals, we see a profound effect on cellular activity, where healthy cells cultured in diseased lung scaffolds adapt and produce proteins further promoting a diseased environment, whereas cells on healthy scaffolds sustain a healthy proteomic profile. Therefore, modulating the environmental context for cell-based therapy may be a potent way to improve treatment using MSCs. In this review, we will describe the importance of the microenvironment for cell-based therapy in chronic lung diseases, how MSC-ECM interactions can affect therapeutic output and describe current progress in the field of cell-based therapy.

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Section: Modulating the 3d Environment For Treatmentmentioning

confidence: 99%

Section: Modulating the 3d Environment For Treatmentmentioning

confidence: 99%

Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

et al. 2021

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“…It has been shown that matrix elasticity regulates the sensitivity of the MSCs to the inflammation in a manner that is dependent on actin polymerization and lipid rafts (Wong et al 2020). Softer matrices support the clustering of TNF-α receptors on the MSC surface by facilitating actin polymerization, which can induce the production of monocyte-regulating chemokines such as CCL2 and CCL7 as well as anti-inflammatory factors such as TSG-6 in higher amounts as compared with a stiffer matrix in response to TNF-α stimulation (Fig.…”

Section: Role Of Biomaterials In Msc-mediated Immunoregulationmentioning

confidence: 99%

Harnessing Dental Stem Cell Immunoregulation Using Cell-Laden Biomaterials

2021

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Successful tissue engineering therapies rely on the appropriate selection of the cell source, biomaterial, and regulatory factors. To be applied in a wide range of clinical applications, the ideal cell source needs to be easily accessible and abundant. Human orofacial tissues and teeth harbor several populations of mesenchymal stem cells (MSCs) with self-renewal and multilineage differentiation capabilities. The ease of access, relative abundance, and minimally invasive isolation procedures needed to harvest most types of the dental-derived MSCs render them a promising cell source for tissue engineering applications. A growing body of evidence has reported the profound immunoregulatory potential of dental-derived MSCs as compared with their bone marrow counterparts. Biomaterials can act as a physical barrier protecting the MSCs from the invasion of the immune system by hindering penetration of proinflammatory cells/cytokines, leading to higher viability of the encapsulated MSCs and improved tissue regeneration. Besides their protective capabilities, biomaterials can actively contribute to the immunoregulatory potential of the MSCs through their physical and chemical properties, including porosity and elasticity. However, despite recent advancement, the therapeutic capability of biomaterials to regulate the MSC–host immune system crosstalk and the mechanism underlying this immunoregulation has been poorly understood. It has been reported that biomaterials can regulate the viability and determine the fate of the encapsulated MSCs through modulation of the NF-kB pathway and the caspase-3 and caspase-8 proapoptotic cascades. Additionally, the physiomechanical properties of the encapsulating biomaterial have been shown to modulate clustering of TNF-α receptors on the encapsulated MSCs while regulating the production of anti-inflammatory factors such as indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) through activation of the P38 MAPK pathway. In the current review, we sought to provide a thorough overview of the immunomodulatory functions of dental-derived MSCs and the role of biomaterials in their interplay with the host immune system.

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“…Even though, the stem cells are features of distinguishable toward the immuno-modulation and immuno-suppression properties. [25][26][27][28] Synergic methods, as well, a promising strategy and biocompatible, biodegradable materials are required for efficient cardiac stem cells transplantation to associate the treatment for AMI. Hence, a pouch-like hydrogel materials like collagen, gelatin, and fibroin can serve as a potential and medically advantageous candidate in drug delivery systems, cell therapy, creation and regeneration of muscle tissues, and controlled release of systems.…”

Section: Introductionmentioning

confidence: 99%

“…Even though, the stem cells are features of distinguishable toward the immuno-modulation and immuno-suppression properties. 25 - 28 …”

Section: Introductionmentioning

confidence: 99%

Synergistic Fabrication of Dose–Response Chitosan/Dextran/β-Glycerophosphate Injectable Hydrogel as Cell Delivery Carrier for Cardiac Healing After Acute Myocardial Infarction

Chen

Liu

Hua³

et al. 2020

Dose-Response

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The human mesenchymal stem cells (hMSCs) therapy offering an encouraging the new methods to establish the conveying on the chitosan (C)/dextran (D)/β-glycerophosphate (β-GP) loaded with hMSCs to enhance the acute myocardial infarctions. The synthesized hMSCs-CD@β-GP system displayed the ratio of determination modules, size of the pore, absorbency, and the swellings ratio in the assortment of the 65 ka, 149 ± 39.8 µm, 92.2%, 42 ± 1.38, and 29 ± 1.9, respectively. The fabricated hMSCs-CD@β-GP was highly stable and physicochemical investigated and confirmed the suitability of the materials for cardiac regeneration applications. The in vitro examinations of the injectable hydrogels with hMSCs-CD@β-GP have recognized that the improved survival rate of the cells, increased the pro-inflammatory expressions factors, pro-angiogenic factors analysis confirmed the promising results of the ejection of fractions, fibrosis area, vessel density with decreased infractions size, with suggesting that the remarkable improvement of the heart regenerative function after myocardial infarctions. The new synergistic approach of the injectable hydrogels with hMSCs could able appropriate for the effective treatment of cardiac therapies after acute myocardial infarctions.

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Soft extracellular matrix enhances inflammatory activation of mesenchymal stromal cells to induce monocyte production and trafficking

Cited by 92 publications

References 62 publications

Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

Harnessing Dental Stem Cell Immunoregulation Using Cell-Laden Biomaterials

Synergistic Fabrication of Dose–Response Chitosan/Dextran/β-Glycerophosphate Injectable Hydrogel as Cell Delivery Carrier for Cardiac Healing After Acute Myocardial Infarction

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