Self-assembling peptides optimize the post-traumatic milieu and synergistically enhance the effects of neural stem cell therapy after cervical spinal cord injury

Zweckberger, Klaus; Ahuja, Christopher S.; Liu, Yang; Wang, Jian; Fehlings, Michael G.

doi:10.1016/j.actbio.2016.06.016

Cited by 97 publications

(67 citation statements)

References 57 publications

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“…Several groups, including our own, have demonstrated histopathological, electrophysiological and functional recovery after subacute transplantation of NSCs from different sources in animal models of subacute SCI[6, 34–36]. Unfortunately, the vast majority of patients are in the chronic phase of their injuries where the glial scar is well-established and has been shown to physically and biochemically interact with migrating cells and outgrowing axons to inhibit regeneration[37–39].…”

Section: Discussionmentioning

confidence: 99%

Neural stem cell mediated recovery is enhanced by Chondroitinase ABC pretreatment in chronic cervical spinal cord injury

et al. 2017

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Traumatic spinal cord injuries (SCIs) affect millions of people worldwide; the majority of whom are in the chronic phase of their injury. Unfortunately, most current treatments target the acute/subacute injury phase as the microenvironment of chronically injured cord consists of a well-established glial scar with inhibitory chondroitin sulfate proteoglycans (CSPGs) which acts as a potent barrier to regeneration. It has been shown that CSPGs can be degraded in vivo by intrathecal Chondroitinase ABC (ChABC) to produce a more permissive environment for regeneration by endogenous cells or transplanted neural stem cells (NSCs) in the subacute phase of injury. Using a translationally-relevant clip-contusion model of cervical spinal cord injury in mice we sought to determine if ChABC pretreatment could modify the harsh chronic microenvironment to enhance subsequent regeneration by induced pluripotent stem cell-derived NSCs (iPS-NSC). Seven weeks after injury—during the chronic phase—we delivered ChABC by intrathecal osmotic pump for one week followed by intraparenchymal iPS-NSC transplant rostral and caudal to the injury epicenter. ChABC administration reduced chronic-injury scar and resulted in significantly improved iPSC-NSC survival with clear differentiation into all three neuroglial lineages. Neurons derived from transplanted cells also formed functional synapses with host circuits on patch clamp analysis. Furthermore, the combined treatment led to recovery in key functional muscle groups including forelimb grip strength and measures of forelimb/hindlimb locomotion assessed by Catwalk. This represents important proof-of-concept data that the chronically injured spinal cord can be ‘unlocked’ by ChABC pretreatment to produce a microenvironment conducive to regenerative iPS-NSC therapy.

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Section: Discussionmentioning

confidence: 99%

Neural stem cell mediated recovery is enhanced by Chondroitinase ABC pretreatment in chronic cervical spinal cord injury

et al. 2017

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“…Furthermore, the activation of astrocytes causes the formation of excessive levels of the extracellular matrix, which, together with an unfriendly environment and the increase of neuronal death, are responsible for the inhibition of cell migration and repair of axonal growth. In this way, large cystic cavities are formed at the site of the injury [21,22].…”

Section: Spinal Cord Injurymentioning

confidence: 99%

Stem Cells Therapy for Spinal Cord Injury: An Overview of Clinical Trials

Silvestro

Bramantı

Trubiani

et al. 2020

IJMS

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Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine. The purpose of this paper is to provide an overview of clinical trials, recorded in clinical trial.gov during 2005–2019, aimed to evaluate the use of stem cell-based therapy in SCI. The results available thus far show the safety and efficacy of stem cell therapy in patients with SCI. However, future trials are needed to investigate the safety and efficacy of stem cell transplantation.

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“…After a primary damage of spinal cord tissue by a direct mechanical force, a series of secondary events involving various pathological responses accelerate the tremendous cell loss, release of cytotoxic factors, and cystic cavitation [1, 2]. Furthermore, excessive extracellular matrices produced by activated astrocytes, called glial scarring, together with the hostile microenvironment, severely inhibit cell migration and axonal regrowth [3]. Although many experimental and clinical studies have been tested, it still lacks effective treatment until now [4–6].…”

Section: Introductionmentioning

confidence: 99%

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

Zhang

2017

Stem Cells International

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Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined. It is important for transplanted cells to migrate into the injured tissue, to survive and undergo neural differentiation, or to play neural protection roles by various mechanisms after SCI. In this review, we will focus on some of the recent knowledge about the biological behavior and function of MSCs in SCI. Meanwhile, we highlight the function of biomaterials to direct the behavior of MSCs based on our series of work on silk fibroin biomaterials and attempt to emphasize combinational strategies such as tissue engineering for functional improvement of SCI.

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Self-assembling peptides optimize the post-traumatic milieu and synergistically enhance the effects of neural stem cell therapy after cervical spinal cord injury

Cited by 97 publications

References 57 publications

Neural stem cell mediated recovery is enhanced by Chondroitinase ABC pretreatment in chronic cervical spinal cord injury

Neural stem cell mediated recovery is enhanced by Chondroitinase ABC pretreatment in chronic cervical spinal cord injury

Stem Cells Therapy for Spinal Cord Injury: An Overview of Clinical Trials

Roles of Mesenchymal Stem Cells in Spinal Cord Injury

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