Extracellular matrix components as therapeutics for spinal cord injury

Haggerty, Agnes E.; Marlow, Megan M.; Oudega, Martin

doi:10.1016/j.neulet.2016.09.053

Cited by 62 publications

(50 citation statements)

References 57 publications

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“…Similar results were reported from 5 patients that received BMMCs, there were no significant adverse effects for 12 months postoperatively and 2 individuals had partial recovery of sexual arousal and somatosensory evoked potentials [103]. Researchers have tested difference biomaterials and cellular sources in preclinical models with promising results, further demonstrating the therapeutic potential of targeting the glial and fibrotic scar after SCI [105].…”

Section: Spinal Cord Injury Therapies Targeting the Glial And Fibrotisupporting

confidence: 65%

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

2018

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Deficits in neuronal function are a hallmark of spinal cord injury (SCI) and therapeutic efforts are often focused on central nervous system (CNS) axon regeneration. However, secondary injury responses by astrocytes, microglia, pericytes, endothelial cells, Schwann cells, fibroblasts, meningeal cells, and other glia not only potentiate SCI damage but also facilitate endogenous repair. Due to their profound impact on the progression of SCI, glial cells and modification of the glial scar are focuses of SCI therapeutic research. Within and around the glial scar, cells deposit extracellular matrix (ECM) proteins that affect axon growth such as chondroitin sulfate proteoglycans (CSPGs), laminin, collagen, and fibronectin. This dense deposition of material, i.e., the fibrotic scar, is another barrier to endogenous repair and is a target of SCI therapies. Infiltrating neutrophils and monocytes are recruited to the injury site through glial chemokine and cytokine release and subsequent upregulation of chemotactic cellular adhesion molecules and selectins on endothelial cells. These peripheral immune cells, along with endogenous microglia, drive a robust inflammatory response to injury with heterogeneous reparative and pathological properties and are targeted for therapeutic modification. Here, we review the role of glial and inflammatory cells after SCI and the therapeutic strategies that aim to replace, dampen, or alter their activity to modulate SCI scarring and inflammation and improve injury outcomes.

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Section: Spinal Cord Injury Therapies Targeting the Glial And Fibrotisupporting

confidence: 65%

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

2018

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“…After SCI, extracellular matrix (ECM) molecules undergo differential regulation, as some, like hyaluronan are degraded, some, like CSPGs, are upregulated and some, like tenascin-C, are newly expressed (Haggerty et al, 2017). These changes lead to the emergence and enrichment of some key inhibitory molecules and eventually make the ECM an inhibitory environment for regeneration after injury.…”

Section: Chondroitin Sulfate Proteoglycansmentioning

confidence: 99%

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Yang

Dai

Chen

et al. 2020

Front. Cell. Neurosci.

162

161

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Recovery from spinal cord injury (SCI) remains an unsolved problem. As a major component of the SCI lesion, the glial scar is primarily composed of scar-forming astrocytes and plays a crucial role in spinal cord regeneration. In recent years, it has become increasingly accepted that the glial scar plays a dual role in SCI recovery. However, the underlying mechanisms of this dual role are complex and need further clarification. This dual role also makes it difficult to manipulate the glial scar for therapeutic purposes. Here, we briefly discuss glial scar formation and some representative components associated with scar-forming astrocytes. Then, we analyze the dual role of the glial scar in a dynamic perspective with special attention to scar-forming astrocytes to explore the underlying mechanisms of this dual role. Finally, taking the dual role of the glial scar into account, we provide several pieces of advice on novel therapeutic strategies targeting the glial scar and scar-forming astrocytes.

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“…YIGSR and IKVAV support neuron attachment, survival and neurite outgrowth in a synergistic manner . Inclusion of peptides from these regions, rather than whole laminin protein, in biomaterial scaffolds increases local density of the bioactive sequence, and possibly biological potency . As scaffolds are constructed from the “bottom‐up”, adding individual bioactive regions of ECM proteins one at a time, they provide the opportunity to isolate the independent and combined effects of specific peptide‐integrin interactions.…”

Section: Introductionmentioning

confidence: 99%

“…61,62 Inclusion of peptides from these regions, rather than whole laminin protein, in biomaterial scaffolds increases local density of the bioactive sequence, and possibly biological potency. 63 As scaffolds are constructed from the "bottom-up", adding individual bioactive regions of ECM proteins one at a time, they provide the opportunity to isolate the independent and combined effects of specific peptide-integrin interactions. Decoupling the effects of different ECM cues will enable creation of tailored, defined matrix environments containing the minimal elements necessary to efficiently direct cell fate.…”

Section: Introductionmentioning

confidence: 99%

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

Seidlits

Liang

Bierman

et al. 2019

J Biomedical Materials Res

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Neural stem/progenitor cell (NS/PC)‐based therapies have shown exciting potential for regeneration of the central nervous system (CNS) and NS/PC cultures represent an important resource for disease modeling and drug screening. However, significant challenges limiting clinical translation remain, such as generating large numbers of cells required for model cultures or transplantation, maintaining physiologically representative phenotypes ex vivo and directing NS/PC differentiation into specific fates. Here, we report that culture of human NS/PCs in 3D, hyaluronic acid (HA)‐rich biomaterial microenvironments increased differentiation toward oligodendrocytes and neurons over 2D cultures on laminin‐coated glass. Moreover, NS/PCs in 3D culture exhibited a significant reduction in differentiation into reactive astrocytes. Many NS/PC‐derived neurons in 3D, HA‐based hydrogels expressed synaptophysin, indicating synapse formation, and displayed electrophysiological characteristics of immature neurons. While inclusion of integrin‐binding, RGD peptides into hydrogels resulted in a modest increase in numbers of viable NS/PCs, no combination of laminin‐derived, adhesive peptides affected differentiation outcomes. Notably, 3D cultures of differentiating NS/PCs were maintained for at least 70 days in medium with minimal growth factor supplementation. In sum, results demonstrate the use of 3D, HA‐based biomaterials for long‐term expansion and differentiation of NS/PCs toward oligodendroglial and neuronal fates, while inhibiting astroglial fates. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 704–718, 2019.

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Extracellular matrix components as therapeutics for spinal cord injury

Cited by 62 publications

References 57 publications

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

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