Modulatory properties of extracellular matrix glycosaminoglycans and proteoglycans on neural stem cells behavior: Highlights on regenerative potential and bioactivity

Shabani, Zahra; Ghadiri, Tahereh; Karimipour, Mohammad; Sadigh‐Eteghad, Saeed; Mahmoudi, Javad; Mehrad, H.; Farhoudi, Mehdi

doi:10.1016/j.ijbiomac.2021.01.006

Cited by 22 publications

(15 citation statements)

References 203 publications

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“… 66 The activity of Reelin is done on the target cells via an engaging Dab‐1 signaling pathway, leading to the activation of vascular endothelial growth factor receptor 2). 60 , 66 , 67 Besides, the increase of NSCs migration into the injured area occurs in the presence of Reelin possibly by the promotion of the Akt/Ras axis. 59 , 68 , 69 The promotion of angiogenesis inside the micelles can provide the vascular bed that is essential for neuronal migration, cortical development, and neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, the critical role of Reelin has been proved in association with neuro‐glia‐vascular regeneration 66 . The activity of Reelin is done on the target cells via an engaging Dab‐1 signaling pathway, leading to the activation of vascular endothelial growth factor receptor 2) 60,66,67 . Besides, the increase of NSCs migration into the injured area occurs in the presence of Reelin possibly by the promotion of the Akt/Ras axis 59,68,69 .…”

Section: Discussionmentioning

confidence: 99%

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Transplantation of bioengineered Reelin‐loadedPLGA/PEGmicelles can accelerate neural tissue regeneration in photothrombotic stroke model of mouse

Shabani

Rahbarghazi‬

Karimipour

et al. 2021

Bioengineering & Transla Med

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Ischemic stroke is characterized by extensive neuronal loss, glial scar formation, neural tissue degeneration that leading to profound changes in the extracellular matrix, neuronal circuitry, and long‐lasting functional disabilities. Although transplanted neural stem cells (NSCs) can recover some of the functional deficit after stroke, retrieval is not complete and repair of lost tissue is negligible. Therefore, the current challenge is to use the combination of NSCs with suitably enriched biomaterials to retain these cells within the infarct cavity and accelerate the formation of a de novo tissue. This study aimed to test the regenerative potential of polylactic‐co‐glycolic acid‐polyethylene glycol (PLGA‐PEG) micelle biomaterial enriched with Reelin and embryonic NSCs on photothrombotic stroke model of mice to gain appropriate methods in tissue engineering. For this purpose, two sets of experiments, either in vitro or in vivo models, were performed. In vitro analyses exhibited PLGA‐PEG plus Reelin‐induced proliferation rate (Ki‐67 + NSCs) and neurite outgrowth (axonization and dendritization) compared to PLGA‐PEG + NSCs and Reelin + NSCs groups ( p < 0.05). Besides, neural differentiation (Map‐2 + cells) was high in NSCs cultured in the presence of Reelin‐loaded PLGA‐PEG micelles ( p < 0.05). Double immunofluorescence staining showed that Reelin‐loaded PLGA‐PEG micelles increased the number of migrating neural progenitor cells (DCX + cells) and mature neurons (NeuN + cells) around the lesion site compared to the groups received PLGA‐PEG and Reelin alone after 1 month ( p < 0.05). Immunohistochemistry results showed that the PLGA/PEG plus Reelin significantly decreased the astrocytic gliosis and increased local angiogenesis (vWF‐positive cells) relative to the other groups. These changes led to the reduction of cavity size in the Reelin‐loaded PLGA‐PEG+NSCs group. Neurobehavioral tests indicated Reelin‐loaded PLGA‐PEG+NSCs promoted neurological outcome and functional recovery ( p < 0.05). These results indicated that Reelin‐loaded PLGA‐PEG is capable of promoting NSCs dynamic growth, neuronal differentiation, and local angiogenesis following ischemic injury via providing a desirable microenvironment. These features can lead to neural tissue regeneration and functional recovery.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transplantation of bioengineered Reelin‐loadedPLGA/PEGmicelles can accelerate neural tissue regeneration in photothrombotic stroke model of mouse

Shabani

Rahbarghazi‬

Karimipour

et al. 2021

Bioengineering & Transla Med

Self Cite

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“…Apart from its supportive role, the brain ECM plays a crucial role in proper neural development, and alterations in its organization are involved in a variety of cortical malformations and other neurodevelopmental disorders [reviewed by Milošević et al (2014)]. Last, the ECM glycosaminoglycans and proteoglycans have been shown to modulate neural stem cell behavior, as it was analytically reviewed by Shabani et al (2021).…”

Section: Ecm Architecture and Physiological Cell Secreted Factorsmentioning

confidence: 99%

3D Reconstitution of the Neural Stem Cell Niche: Connecting the Dots

Ioannidis

Angelopoulos

Gakis

et al. 2021

Front. Bioeng. Biotechnol.

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Neural stem cells (NSCs) are important constituents of the nervous system, and they become constrained in two specific regions during adulthood: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. The SVZ niche is a limited-space zone where NSCs are situated and comprised of growth factors and extracellular matrix (ECM) components that shape the microenvironment of the niche. The interaction between ECM components and NSCs regulates the equilibrium between self-renewal and differentiation. To comprehend the niche physiology and how it controls NSC behavior, it is fundamental to develop in vitro models that resemble adequately the physiologic conditions present in the neural stem cell niche. These models can be developed from a variety of biomaterials, along with different biofabrication approaches that permit the organization of neural cells into tissue-like structures. This review intends to update the most recent information regarding the SVZ niche physiology and the diverse biofabrication approaches that have been used to develop suitable microenvironments ex vivo that mimic the NSC niche physiology.

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“…Proteoglycans are capable of sequestering water molecules and establishing swelling pressure via hydrophilic GAG, thereby providing mechanical strength against compressive forces. In addition, proteoglycans play pivotal developmental and homeostatic functions in both extracellular matrix organization 1 and cell behaviour regulation 2 – 4 by deploying various growth factors (e.g., TGF-β 5 and FGF 6 ), cytokines (e.g., interleukin-10 7 and CCL5 8 ), and other distinct signalling molecules (e.g., hedgehogs 9 and STING 10 ) via their chemical binding to GAGs.…”

Section: Introductionmentioning

confidence: 99%

Integration of a miniaturized DMMB assay with high-throughput screening for identifying regulators of proteoglycan metabolism

Sun

Tsui

et al. 2022

Sci Rep

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Defective biosynthesis or function of proteoglycans causes pathological conditions in a variety of tissue systems. Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by progressive cartilage destruction caused by imbalanced proteoglycan synthesis and degradation. Identifying agents that regulate proteoglycan metabolism may benefit the development of OA-modifying therapeutics. High-throughput screening (HTS) of chemical libraries has paved the way for achieving this goal. However, the implementation and adaptation of HTS assays based on proteoglycan measurement remain underexploited. Using primary porcine chondrocytes as a model, we report a miniaturized dimethyl-methylene blue (DMMB) assay, which is commonly used to quantitatively evaluate sulfated glycosaminoglycan (GAG) content, with an optimized detection range and reproducibility and its integration with HTS. Treatment with TGF-β1 and IL1-α, known as positive and negative proteoglycan regulators, respectively, supported the assay specificity. A pre-test of chemical screening of 960 compounds identified both stimulators (4.48%) and inhibitors (6.04%) of GAG production. Fluorophore-assisted carbohydrate electrophoresis validated the activity of selected hits on chondroitin sulfate expression in an alginate culture system. Our findings support the implementation of this simple colorimetric assay in HTS to discover modifiers of OA or other diseases related to dysregulated proteoglycan metabolism.

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Modulatory properties of extracellular matrix glycosaminoglycans and proteoglycans on neural stem cells behavior: Highlights on regenerative potential and bioactivity

Cited by 22 publications

References 203 publications

Transplantation of bioengineered Reelin‐loadedPLGA/PEGmicelles can accelerate neural tissue regeneration in photothrombotic stroke model of mouse

Transplantation of bioengineered Reelin‐loadedPLGA/PEGmicelles can accelerate neural tissue regeneration in photothrombotic stroke model of mouse

3D Reconstitution of the Neural Stem Cell Niche: Connecting the Dots

Integration of a miniaturized DMMB assay with high-throughput screening for identifying regulators of proteoglycan metabolism

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