Boundary Cap Neural Crest Stem Cell Transplants Contribute Mts1/S100A4-Expressing Cells in the Glial Scar

Trolle, Carl; Ivert, Patrik; Hoeber, Jan; Rocamonde-Lago, Iris; Vasylovska, Svitlana; Lukanidin, Eugen; Kozlova, Elena N.

doi:10.2217/rme-2016-0163

Cited by 3 publications

(8 citation statements)

References 52 publications

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“…To clarify the contribution of S100A4 to the formation of a glial scar and its role in supporting the regeneration of sensory axons, Trolle and coauthors administered boundary cap neural crest stem cells, known to support the growth of sensory axons during development, to a murine model of dorsal root injury. They demonstrated that the stem cells, although forming permissive gaps in the glial scar, differentiated into non-permissive S100A4-expressing astrocytes that did not contribute to the regeneration of sensory axons [24]. These data confirmed the induction of high levels of S100A4, particularly in WM astrocytes after sciatic nerve or dorsal root injury [35,76] and indicated a role for S100A4 in the formation of glia scar after injury in the spinal cord.…”

Section: Acute Injuriesmentioning

confidence: 80%

“…Spatially, the presence of S100A4 in the rodent nervous system has been detected mainly in CNS myelinated areas as the olfactory tract, optic nerve, corpus callosum, internal capsule, fimbria, and spinal cord funiculi. However, the protein was also found in several nonmyelinated or poorly myelinated areas, such as the pituitary gland, the olfactory bulb and Lissauer's tract [22,24].…”

Section: S100a4 In the Nervous System Physiologymentioning

confidence: 99%

“…Notwithstanding the neuroprotective effects of S100A4 in acute brain stress [70], it was observed the protein represents a specific marker for WM astrocytes [21] and can influence the formation of a "non-permissive" glial scar following nerve injuries, therefore limiting axonal regeneration. In this aspect, S100A4 was found markedly overexpressed mainly in WM astrocytes adjacent to the site of transection in the spinal cord after sciatic nerve or dorsal root resection [21,24], suggesting its participation in the formation of a "non-permissive" environment [24]. It is well-known that WM astrocytes are key players in the development of a glial scar that appears following injury and that represents a major limit for efficient axonal growth and remyelination by oligodendrocytes [73,74].…”

Section: Acute Injuriesmentioning

confidence: 99%

“…S100A4 is expressed in both the central (CNS) and peripheral nervous system (PNS), where it is found in glial cells and satellite cells, as well as in neurons, in particular in cell subpopulations belonging to dorsal root ganglia (DRG), sympathetic neurons, trigeminal, geniculate and nodose ganglion cells [21][22][23][24][25]. Spatially, the presence of S100A4 in the rodent nervous system has been detected mainly in CNS myelinated areas as the olfactory tract, optic nerve, corpus callosum, internal capsule, fimbria, and spinal cord funiculi.…”

Section: S100a4 In the Nervous System Physiologymentioning

confidence: 99%

“…Although only a few populations of neurons express S100A4 [21][22][23][24], many types of neuronal cells can instead respond to extracellular S100A4, as they possess different receptor types or interactors capable of binding S100A4. The possible effects of S100A4 on neuron survival and neurite outgrowth were assessed in different primary neuronal cultures and with several experimental paradigms, ranging from direct exogenous S100A4 administration, to neuron-astrocytes co-cultures.…”

Section: Neuronal Cellsmentioning

confidence: 99%

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S100A4 in the Physiology and Pathology of the Central and Peripheral Nervous System

D’Ambrosi

Milani

Apolloni

2021

Cells

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S100A4 is a member of the large family of S100 proteins, exerting a broad range of intracellular and extracellular functions that vary upon different cellular contexts. While S100A4 has long been implicated mainly in tumorigenesis and metastatization, mounting evidence shows that S100A4 is a key player in promoting pro-inflammatory phenotypes and organ pro-fibrotic pathways in the liver, kidney, lung, heart, tendons, and synovial tissues. Regarding the nervous system, there is still limited information concerning S100A4 presence and function. It was observed that S100A4 exerts physiological roles contributing to neurogenesis, cellular motility and chemotaxis, cell differentiation, and cell-to cell communication. Furthermore, S100A4 is likely to participate to numerous pathological processes of the nervous system by affecting the functions of astrocytes, microglia, infiltrating cells and neurons and thereby modulating inflammation and immune reactions, fibrosis as well as neuronal plasticity and survival. This review summarizes the current state of knowledge concerning the localization, deregulation, and possible functions of S100A4 in the physiology of the central and peripheral nervous system. Furthermore, we highlight S100A4 as a gene involved in the pathogenesis of neurological disorders such as brain tumors, neurodegenerative diseases, and acute injuries.

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Section: Acute Injuriesmentioning

confidence: 80%

Section: S100a4 In the Nervous System Physiologymentioning

confidence: 99%

Section: Acute Injuriesmentioning

confidence: 99%

Section: S100a4 In the Nervous System Physiologymentioning

confidence: 99%

Section: Neuronal Cellsmentioning

confidence: 99%

See 3 more Smart Citations

S100A4 in the Physiology and Pathology of the Central and Peripheral Nervous System

D’Ambrosi

Milani

Apolloni

2021

Cells

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Boundary cap neural crest stem cells promote angiogenesis after transplantation to avulsed dorsal roots in mice and induce migration of endothelial cells in 3D printed scaffolds

Trolle,

Han,

Mutt

et al. 2024

Neuroscience Letters

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Dorsal Root Injury—A Model for Exploring Pathophysiology and Therapeutic Strategies in Spinal Cord Injury

Aldskogius

Kozlova

2021

Cells

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Unraveling the cellular and molecular mechanisms of spinal cord injury is fundamental for our possibility to develop successful therapeutic approaches. These approaches need to address the issues of the emergence of a non-permissive environment for axonal growth in the spinal cord, in combination with a failure of injured neurons to mount an effective regeneration program. Experimental in vivo models are of critical importance for exploring the potential clinical relevance of mechanistic findings and therapeutic innovations. However, the highly complex organization of the spinal cord, comprising multiple types of neurons, which form local neural networks, as well as short and long-ranging ascending or descending pathways, complicates detailed dissection of mechanistic processes, as well as identification/verification of therapeutic targets. Inducing different types of dorsal root injury at specific proximo-distal locations provide opportunities to distinguish key components underlying spinal cord regeneration failure. Crushing or cutting the dorsal root allows detailed analysis of the regeneration program of the sensory neurons, as well as of the glial response at the dorsal root-spinal cord interface without direct trauma to the spinal cord. At the same time, a lesion at this interface creates a localized injury of the spinal cord itself, but with an initial neuronal injury affecting only the axons of dorsal root ganglion neurons, and still a glial cell response closely resembling the one seen after direct spinal cord injury. In this review, we provide examples of previous research on dorsal root injury models and how these models can help future exploration of mechanisms and potential therapies for spinal cord injury repair.

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Boundary Cap Neural Crest Stem Cell Transplants Contribute Mts1/S100A4-Expressing Cells in the Glial Scar

Abstract: bNCSC transplants contribute nonpermissive Mts1/S100A4-expressing cells to the glial scar after dorsal root avulsion.

Cited by 3 publications

References 52 publications

S100A4 in the Physiology and Pathology of the Central and Peripheral Nervous System

S100A4 in the Physiology and Pathology of the Central and Peripheral Nervous System

Boundary cap neural crest stem cells promote angiogenesis after transplantation to avulsed dorsal roots in mice and induce migration of endothelial cells in 3D printed scaffolds

Dorsal Root Injury—A Model for Exploring Pathophysiology and Therapeutic Strategies in Spinal Cord Injury

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