Combination therapy with astaxanthin and epidermal neural crest stem cells improves motor impairments and activates mitochondrial biogenesis in a rat model of spinal cord injury

Shalmani, Leila Mohaghegh; Valian, Neda; Pournajaf, Safura; Abbaszadeh, Fatemeh; Dargahi, Leila; Jorjani, Masoumeh

doi:10.1016/j.mito.2020.03.002

Cited by 17 publications

(13 citation statements)

References 47 publications

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“…Axon regeneration does not occur due to the nonresponsive environment of the injured spinal cord. Emerging evidence suggests that NCLSCs derived from various adult tissues may serve a promising strategy for SCI 111‐113 . Recently, human dental pulp (hDP)‐NCSCs were used to evaluate the effect of hDP‐NCSC delivery on the lesion site and functional recovery after SCI 111 .…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, hDP‐NCSCs can provide a new cell source and therapy for SCI 111 . Apart from hDP‐NCSCs, transplanted EPI‐NCSCs were shown to not only provide neurotrophic support in an ex vivo SCI contusion model, 112 but also improve motor function after SCI in rats, in particular demonstrating beneficial synergistic effects when delivered in combination with the potent antioxidant Astaxanthin 113 . These findings suggest that further research into combinatorial strategies with EPI‐NCSCs and pharmaceutical agents may prove to be valuable for the treatment of SCI.…”

Section: Introductionmentioning

confidence: 99%

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Neural crest-like stem cells for tissue regeneration

Soto

Ding

Wang

et al. 2021

Stem Cells Translational Medicine

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Neural crest stem cells (NCSCs) are a transient population of cells that arise during early vertebrate development and harbor stem cell properties, such as self‐renewal and multipotency. These cells form at the interface of non‐neuronal ectoderm and neural tube and undergo extensive migration whereupon they contribute to a diverse array of cell and tissue derivatives, ranging from craniofacial tissues to cells of the peripheral nervous system. Neural crest‐like stem cells (NCLSCs) can be derived from pluripotent stem cells, placental tissues, adult tissues, and somatic cell reprogramming. NCLSCs have a differentiation capability similar to NCSCs, and possess great potential for regenerative medicine applications. In this review, we present recent developments on the various approaches to derive NCLSCs and the therapeutic application of these cells for tissue regeneration.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neural crest-like stem cells for tissue regeneration

Soto

Ding

Wang

et al. 2021

Stem Cells Translational Medicine

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“…15 Accordingly, they can significantly contribute to the recovery of sensory and motor functions in a mouse and rat model of spinal cord injury. [16][17][18] In addition, transplantation of hair follicle stem cells supports the repair of peripheral nerve defects [19][20][21] and has benefits in a rat model of ischemic stroke. 22,23 Nowadays, several strategies are employed to comply with large-scale production of stem cells and their derivatives in the most efficient fashion possible to maximize their therapeutic effects.…”

Section: Introductionmentioning

confidence: 99%

“…These stem cells can differentiate into various cell types, such as neurons 7–11 and glial cells, 12–14 and express a variety of neurotrophic factors 15 . Accordingly, they can significantly contribute to the recovery of sensory and motor functions in a mouse and rat model of spinal cord injury 16–18 . In addition, transplantation of hair follicle stem cells supports the repair of peripheral nerve defects 19–21 and has benefits in a rat model of ischemic stroke 22,23 …”

Section: Introductionmentioning

confidence: 99%

The beneficial effects of chick embryo extract preconditioning on hair follicle stem cells: A promising strategy to generate Schwann cells

et al. 2023

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The beneficial effects of hair follicle stem cells in different animal models of nervous system conditions have been extensively studied. While chick embryo extract (CEE) has been used as a growth medium supplement for these stem cells, this is the first study to show the effect of CEE on them. The rat hair follicle stem cells were isolated and supplemented with 10% fetal bovine serum plus 10% CEE. The migration rate, proliferative capacity and multipotency were evaluated along with morphometric alteration and differentiation direction. The proteome analysis of CEE content identified effective factors of CEE that probably regulate fate and function of stem cells. The CEE enhances the migration rate of stem cells from explanted bulges as well as their proliferation, likely due to activation of AP‐1 and translationally controlled tumour protein (TCTP) by thioredoxin found in CEE. The increased length of outgrowth may be the result of cyclic AMP response element binding protein (CREB) phosphorylation triggered by active CamKII contained in CEE. Further, CEE supplementation upregulates the expression of vascular endothelial growth factor (VEGF), brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor. The elevated expression of target genes and proteins may be due to CREB, AP‐1 and c‐Myc activation in these stem cells. Given the increased transcript levels of neurotrophins, VEGF, and the expression of PDGFR‐α, S100B, MBP and SOX‐10 protein, it is possible that CEE promotes the fate of these stem cells towards Schwann cells.

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“…They can be extracted from bulge hair follicle in adulthood for autologous application, avoiding graft rejection and lack of donor [29]. Transplantation of EPI-NCSCs into injured rat spinal cords can improve locomotor and sensory function by expressing neurotrophic factors, angiogenic factors and extracellular proteases [30,31]. Although EPI-NCSCs-CM has been studied for regenerative therapy [32,33], few studies have explored its potential for neuronal repairing after SCI.…”

Section: Introductionmentioning

confidence: 99%

Conditioned medium of epidermal neural crest stem cells improved functional recovery and tissue repairing after spinal cord injury by suppressing neuronal apoptosis through the PI3K/AKT signaling pathway

Ma,

Liu,

Liu

et al. 2023

Preprint

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Aims: This study evaluated the effects of conditioned medium from epidermal neural crest stem cells (EPI-NCSCs-CM) on functional recovery after spinal cord injury (SCI) and investigated the role of PI3K-AKT signaling pathway in regulating the neuronal apoptosis. Methods: EPI-NCSCs were isolated from 10-day-old rats and cultured for 48 hours and EPI-NCSCs-CM was extracted. H2O2 was used to establish apoptosis model in SHSY-5Y cells. Cell viability and survival rate were assessed using CCK-8 assay and Calcein-AM/PI staining. A SCI contusion model was established in adult Sprague-Dawley rats. Functional recovery was evaluated using the Basso-Bresnahan-Beattie (BBB) scoring system, inclined test, and footprint observation. Electrophysiological recording was used to analyze neurological restoration after SCI. Histological organization was assessed using Hematoxylin-eosin (H&E) staining and Nissl staining. TUNEL staining and ROS detection were applied to measure the apoptosis and oxidative stress levels. Western blot was conducted to detect the expression levels of apoptosis markers and PI3K/AKT signaling-related proteins. Results: EPI-NCSCs-CM significantly promoted functional and histological rehabilitation in SCI rats by suppressing neuronal apoptosis through regulating PI3K/AKT signaling pathway. In vitro study indicated that EPI-NCSCs-CM administration alleviated neurotoxicity caused by H2O2 in SHSY-5Y cells. The administration of LY294002 (a PI3K inhibitor) implied that the PI3K/AKT signaling pathway plays a vital role in regulating neuronal apoptosis. Conclusions: This study presents a new strategy for repairing SCI using EPI-NCSCs-CM, and provides evidence that EPI-NCSCs-CM can inhibit neuronal apoptosis by regulating the PI3K/AKT signaling pathway in SCI rats.

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Combination therapy with astaxanthin and epidermal neural crest stem cells improves motor impairments and activates mitochondrial biogenesis in a rat model of spinal cord injury

Cited by 17 publications

References 47 publications

Neural crest-like stem cells for tissue regeneration

Neural crest-like stem cells for tissue regeneration

The beneficial effects of chick embryo extract preconditioning on hair follicle stem cells: A promising strategy to generate Schwann cells

Conditioned medium of epidermal neural crest stem cells improved functional recovery and tissue repairing after spinal cord injury by suppressing neuronal apoptosis through the PI3K/AKT signaling pathway

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