Poly(γ-Glutamic Acid) as an Exogenous Promoter of Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells

Antunes, Joana C.; Tsaryk, Roman; Rm, Gonçalves; Cl, Pereira; Landes, Constantin A.; Brochhausen, Christoph; Ghanaati, Shahram; Barbosa, Mário A.; Kirkpatrick, Charles James

doi:10.1089/ten.tea.2014.0386

Cited by 13 publications

(9 citation statements)

References 95 publications

(166 reference statements)

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“…These results support previous evidences from our group, demonstrating that c-PGA promotes chondrogenesis of MSCs in vitro, enhancing Col II, Agg and Sox-9 early expression [55]. This effect was partially observed in IVD organ cultures [50].…”

Section: Discussionsupporting

confidence: 92%

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc

et al. 2016

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Section: Discussionsupporting

confidence: 92%

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc

et al. 2016

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“…In the present work, a decrease in DHI, as well as loss of proteoglycan content and of NP-AF border integrity were observed in all groups. Although γ-PGA and Ch/γ-PGA NCs were shown to promote cartilaginous ECM production in vitro and ex vivo [32,33], this was not confirmed in vivo, possibly due to the much higher injection/NP volume ratio in the rat than in the bovine [34]. We also cannot exclude the presence of the immune system in vivo, which was absent in previous studies [34].…”

Section: Discussionmentioning

confidence: 60%

Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments

Cunha

Teixeira

Ribeiro-Machado

et al. 2020

IJMS

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Inflammation is central in intervertebral disc (IVD) degeneration/regeneration mechanisms, and its balance is crucial to maintain tissue homeostasis. This work investigates the modulation of local and systemic inflammatory response associated with IVD degeneration/herniation by administration of PRO-versus ANTI-inflammatory treatments. Chitosan/poly-γ-glutamic acid nanocomplexes, known as pro-inflammatory (PRO), and soluble diclofenac, a non-steroidal anti-inflammatory drug (ANTI), were intradiscally administered in a rat IVD injury model, 24 h after lesion. Two weeks after administration, a reduction of disc height accompanied by hernia formation was observed. In the PRO-inflammatory treated group, IL-1β, IL-6 and COX-2 IVD gene expression were upregulated, and loss of nucleus pulposus (NP) structure and composition was observed. Systemically, lower T-cell frequency was observed in the lymph nodes (LN) and spleen (SP) of the PRO group, together with an increase in CD4+ T cells subset in the blood (BL) and LN. In contrast, the ANTI-group had higher proteoglycans/collagen ratio and collagen type 2 content in the NP, while an increase in the frequency of myeloid cells, M1 macrophages and activated macrophages (MHCII+) was observed at the systemic level. Overall, this study illustrates the dynamics of local and systemic inflammatory and immune cell responses associated with intradiscal therapies, which will contribute to designing more successful immunomodulatory treatments for IVD degeneration.Several in vivo models of IVD degeneration are described in the literature, with murine tail models of mechanical injury by needle puncture commonly used [4,5]. Depending on the needle size, the puncture may induce annulus fibrosus (AF) disruption while causing depressurization of the nucleus pulposus (NP) [6,7]. Needle calibers, varying between 16 to 22 G, often lead to significant pressure failure, decreased cell viability, increased expression of pro-inflammatory/degenerative factors and alterations in extracellular matrix (ECM) composition in IVDs from both large (e.g., bovine [8]) and small animals (e.g., rabbit [9] and rat [10]), resembling human IVD degeneration. Our group has previously established and validated an IVD herniation/degeneration model of rat caudal needle puncture, using a 21 G needle [10,11], in which IVD herniation and infiltration of macrophages were observed [10]. This model is relatively simple to manipulate and presents cost-effectiveness [12]. Moreover, it allows the study of local and systemic immune response, crucial in human IVD degeneration and difficult to analyze in vitro or ex vivo [13]. Only a few studies, mainly in bone, address the dialogue/interplay between local/systemic immune responses and how this can be linked with tissue remodeling [14,15]. Despite this, it is important to consider the limitations of small animal models of IVD degeneration when compared to humans, such as differences in spine biomechanics, IVD size and cellular composition, which may be critical for clinical trans...

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“…Synthetic polymers as building blocks for ECM mimics are more easily available . Representative polymers are poly(ethylene glycol) (PEG), , polylactic acid (PLA), , polyglutamic acid (PGA), , and poly(ethylene oxide) (PEO). , One of the significant advantages of synthetic ECM mimics is the precise controllability and readily tunable mechanical properties. Double-network hydrogels possessing high mechanical strength and toughness have drawn increasing attention as biological tissue mimics. − Synthetic polymers usually lack supporting cues for cell contacts.…”

Section: Ecm Mimicsmentioning

confidence: 99%

Constructing ECM-like Structure on the Plasma Membrane via Peptide Assembly to Regulate the Cellular Response

Song

Zhang

et al. 2022

Langmuir

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This feature article introduces the design of self-assembling peptides that serve as the basic building blocks for the construction of extracellular matrix (ECM)-like structure in the vicinity of the plasma membrane. By covalently conjugating a bioactive motif, such as membrane protein binding ligand or enzymatic responsive building block, with a self-assembling motif, especially the aromatic peptide, a self-assembling peptide that retains bioactivity is obtained. Instructed by the target membrane protein or enzyme, the bioactive peptides self-assemble into ECM-like structure exerting various stimuli to regulate the cellular response via intracellular signaling, especially mechanotransduction. By briefly summarizing the properties and applications (e.g., wound healing, controlling cell motility and cell fate) of these peptides, we intend to illustrate the basic requirements and promises of the peptide assembly as a true bottom-up approach in the construction of artificial ECM.

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Poly(γ-Glutamic Acid) as an Exogenous Promoter of Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells

Cited by 13 publications

References 95 publications

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc

Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments

Constructing ECM-like Structure on the Plasma Membrane via Peptide Assembly to Regulate the Cellular Response

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