Axonal outgrowth stimulation after alginate/mesenchymal stem cell therapy in injured rat spinal cord

Blasko, Juraj; Szekiova, Eva; Slovinská, Lucia; Kafka, Jozef; Cizkova, Dasa

doi:10.21307/ane-2017-066

Cited by 18 publications

(12 citation statements)

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“…In fact, scaffolds promote MSC adhesion and their survival. The effects of cell-seeded biomaterial scaffolds on improved axonal regrowth or enhanced functional outcomes after SCI than scaffolds alone have been shown in many studies ( Hejcl et al, 2010 ; Kim et al, 2016 ; Blasko et al, 2017 ; Peng et al, 2018 ; Zaviskova et al, 2018 ) and reviewed in Libro et al (2017) and Yousefifard et al (2019) .…”

Section: Biomaterials In Combination With Mscs In Sci Treatmentmentioning

confidence: 99%

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

Syková

Cizkova

Kubinová

2021

Front. Cell Dev. Biol.

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Preclinical and clinical studies with various stem cells, their secretomes, and extracellular vesicles (EVs) indicate their use as a promising strategy for the treatment of various diseases and tissue defects, including neurodegenerative diseases such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). Autologous and allogenic mesenchymal stem cells (MSCs) are so far the best candidates for use in regenerative medicine. Here we review the effects of the implantation of MSCs (progenitors of mesodermal origin) in animal models of SCI and ALS and in clinical studies. MSCs possess multilineage differentiation potential and are easily expandable in vitro. These cells, obtained from bone marrow (BM), adipose tissue, Wharton jelly, or even other tissues, have immunomodulatory and paracrine potential, releasing a number of cytokines and factors which inhibit the proliferation of T cells, B cells, and natural killer cells and modify dendritic cell activity. They are hypoimmunogenic, migrate toward lesion sites, induce better regeneration, preserve perineuronal nets, and stimulate neural plasticity. There is a wide use of MSC systemic application or MSCs seeded on scaffolds and tissue bridges made from various synthetic and natural biomaterials, including human decellularized extracellular matrix (ECM) or nanofibers. The positive effects of MSC implantation have been recorded in animals with SCI lesions and ALS. Moreover, promising effects of autologous as well as allogenic MSCs for the treatment of SCI and ALS were demonstrated in recent clinical studies.

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Section: Biomaterials In Combination With Mscs In Sci Treatmentmentioning

confidence: 99%

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

Syková

Cizkova

Kubinová

2021

Front. Cell Dev. Biol.

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“…From a neurodegenerative perspective, it has become increasingly recognized that neuroinflammation plays a significant pathomechanistic role [51]. [53]. Antagonizing the inductive effect of myelin oligodendrocyte glycoprotein (MOG), MSCs-derived exosomes suppress neuroinflammation and show anti-neuroinflammatory and autoimmune suppressive characteristics after SCI.…”

Section: Secretome Of Mscs and Suppression Of Neuroinflammationmentioning

confidence: 99%

“…Besalti et al demonstrated that an early intravenous administration of allogenic MSCs would up-regulate the expression of GFAP by seven days after injury[121]. MSCs transplantation contributes to the formation of a neuroprotective microenvironment by GFAPexpressing astrocytes for neurogenesis[53]. It has been shown that reactive and hypertrophic astrocytes start expressing COX-2 within the area of ischemia in response to pro-inflammatory stimuli[122].…”

mentioning

confidence: 99%

Biomaterial-supported MSCs transplantation enhances cell-cell communication for spinal cord injury

Wang

yang

2020

Preprint

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The spinal cord is part of the central nervous system (CNS) and serves to connect the brain to the peripheral nervous system and peripheral tissues. The cell types that primarily comprise the spinal cord are neurons and several categories of glia, including astrocytes, oligodendrocytes, and microglia. Ependymal cells and small populations of endogenous stem cells, such as oligodendrocyte progenitor cells, also reside in the spinal cord [1]. Neurons are interconnected in circuits; those that process cutaneous sensory input are mainly located in the dorsal spinal cord, while those involved in proprioception and motor control are predominately located in the ventral spinal cord [2]. Due to the importance of the spinal cord, neurodegenerative disorders and traumatic injuries affecting the spinal cord will lead to motor deficits and loss of sensory inputs. Spinal cord injury (SCI), resulting in paraplegia and tetraplegia as a result of deleterious interconnected mechanisms encompassed by the primary and secondary injury, represents a heterogeneously behavioral and cognitive deficit that remains incurable. Following SCI, various barriers containing the neuroinflammation, neural tissue defect (neurons, microglia, astrocytes, and oligodendrocytes), cavity formation, loss of neuronal circuitry and function must be overcame[3]. Notably, the pro -inflammatory and anti-inflammatory effect s of cell-cell communication networks play critical roles in homeostatic, driving the pathophysiologic and consequent cognitive outcomes. In the spinal cord, astrocytes, oligodendrocytes and microglia are involved in not only development but also pathology. Glial cells play dual roles (negative vs. positive effects) in these processes. After SCI, detrimental effects usually dominate and significantly retard functional recovery, and curbing these effects is critical for promoting neurological improvement. Indeed, residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (macrophages and neutrophils), activated by SCI, give rise to full-blown inflammatory cascades. These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit[4]. Given the various multifaceted obstacles in SCI treatment, a combinatorial therapy of cell transplantation and biomaterial implantation may be addressed in detail here. For the sake of preserving damaged tissue integrity and providing physical support and trophic supply for axon regeneration, MSCs transplantation has come to the front stage in therapy for SCI with the constant progress of stem cell engineering [5]. MSCs transplantation promotes scaffold integration and regenerative growth potential. Integrating into the implanted scaffold, MSCs influences implant integration by improving the healing process[6]. Conversely, biomaterial scaffolds offer MSCs with a sheltered microenvironment from the surrounding pathological changes, in addition to bridging connection spinal cord stump and offering physical and directional support for axonal regeneration. Besides, Biomaterial scaffolds mimic the extracellular matrix to suppress immune responses. Here, we review the advances in combinatorial biomaterial scaffolds and MSCs transplantation approach that targets certain aspects of various intercellular communications in the pathologic process following SCI. Finally, the challenges of biomaterial-supported MSCs transplantation and its future direction for neuronal regeneration will be presented.

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“…Much larger doses of cell transplantation are needed to treat the restrictions of selective permeability of the endothelium on cell infiltration. To circumvent this limitation, dual therapies including stem cells administered with the biomaterial, astrocyte-derived conditioned medium or drugs that transiently open the BBB have been considered [ 47 ]. Antagonizing the inductive effect of myelinoligodendrocyte glycoprotein (MOG), MSC-derived exosomes suppress neuroinflammation and show anti-neuroinflammatory and autoimmune suppressive characteristics after SCI.…”

Section: Introductionmentioning

confidence: 99%

“…Besalti et al demonstrated that an early intravenous administration of allogenic MSCs would upregulate the expression of GFAP by 7 days after injury [ 115 ]. MSC transplantation contributes to the formation of a neuroprotective microenvironment by GFAP-expressing astrocytes for neurogenesis [ 47 ]. It has been shown that reactive and hypertrophic astrocytes start expressing COX-2 within the area of ischemia in response to pro-inflammatory stimuli [ 116 ].…”

Section: Introductionmentioning

confidence: 99%

Biomaterial-supported MSC transplantation enhances cell–cell communication for spinal cord injury

Zhang

Yuan

et al. 2021

Stem Cell Res Ther

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The spinal cord is part of the central nervous system (CNS) and serves to connect the brain to the peripheral nervous system and peripheral tissues. The cell types that primarily comprise the spinal cord are neurons and several categories of glia, including astrocytes, oligodendrocytes, and microglia. Ependymal cells and small populations of endogenous stem cells, such as oligodendrocyte progenitor cells, also reside in the spinal cord. Neurons are interconnected in circuits; those that process cutaneous sensory input are mainly located in the dorsal spinal cord, while those involved in proprioception and motor control are predominately located in the ventral spinal cord. Due to the importance of the spinal cord, neurodegenerative disorders and traumatic injuries affecting the spinal cord will lead to motor deficits and loss of sensory inputs.Spinal cord injury (SCI), resulting in paraplegia and tetraplegia as a result of deleterious interconnected mechanisms encompassed by the primary and secondary injury, represents a heterogeneously behavioral and cognitive deficit that remains incurable. Following SCI, various barriers containing the neuroinflammation, neural tissue defect (neurons, microglia, astrocytes, and oligodendrocytes), cavity formation, loss of neuronal circuitry, and function must be overcame. Notably, the pro-inflammatory and anti-inflammatory effects of cell–cell communication networks play critical roles in homeostatic, driving the pathophysiologic and consequent cognitive outcomes. In the spinal cord, astrocytes, oligodendrocytes, and microglia are involved in not only development but also pathology. Glial cells play dual roles (negative vs. positive effects) in these processes. After SCI, detrimental effects usually dominate and significantly retard functional recovery, and curbing these effects is critical for promoting neurological improvement. Indeed, residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (macrophages and neutrophils), activated by SCI, give rise to full-blown inflammatory cascades. These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit.Given the various multifaceted obstacles in SCI treatment, a combinatorial therapy of cell transplantation and biomaterial implantation may be addressed in detail here. For the sake of preserving damaged tissue integrity and providing physical support and trophic supply for axon regeneration, MSC transplantation has come to the front stage in therapy for SCI with the constant progress of stem cell engineering. MSC transplantation promotes scaffold integration and regenerative growth potential. Integrating into the implanted scaffold, MSCs influence implant integration by improving the healing process. Conversely, biomaterial scaffolds offer MSCs with a sheltered microenvironment from the surrounding pathological changes, in addition to bridging connection spinal cord stump and offering physical and directional support for axonal regeneration. Besides, Biomaterial scaffolds mimic the extracellular matrix to suppress immune responses.Here, we review the advances in combinatorial biomaterial scaffolds and MSC transplantation approach that targets certain aspects of various intercellular communications in the pathologic process following SCI. Finally, the challenges of biomaterial-supported MSC transplantation and its future direction for neuronal regeneration will be presented.

show abstract

Axonal outgrowth stimulation after alginate/mesenchymal stem cell therapy in injured rat spinal cord

Cited by 18 publications

References 50 publications

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

Biomaterial-supported MSCs transplantation enhances cell-cell communication for spinal cord injury

Biomaterial-supported MSC transplantation enhances cell–cell communication for spinal cord injury

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