Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury

Pereira, Inês M.; Marote, Ana; Salgado, António J.; Silva, Nuno

doi:10.3390/ph12020065

Cited by 73 publications

(72 citation statements)

References 185 publications

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“…To date, three main sources of NSCs have been described: direct isolation from the primary CNS tissue (either from the foetal or adult brain), differentiation from pluripotent stem cells, and transdifferentiation from somatic cells. Notably, iPSC-derived NSCs have striking advantages over ESCderived NSCs, namely, the possibility of autologous transplantation [24] . Recent investigations have also examined the utility of MSCs recovered from tissues other than the bone marrow, including the umbilical cord and adipose tissue [25] .…”

Section: Discussionmentioning

confidence: 99%

HiPSC-Derived NSCs Effectively Promote The Functional Recovery of Acute Spinal Cord Injury in Mice

Kong

Feng

Asiamah

et al. 2020

Preprint

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Background: Spinal cord injury (SCI) is a common disease that results in motor and sensory disorders and even lifelong paralysis. The transplantation of stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), or subsequently generated stem/progenitor cells, is predicted to be a promising treatment for SCI. In this study, we aimed to investigate effect of human iPSC-derived neural stem cells (hiPSC-NSCs) and umbilical cord-derived MSCs (huMSCs) in a mouse model of acute SCI. Methods: Acute SCI mice model were established and were randomly treated as PBS (control group), repaired with 1×105 hiPSC-NSCs (NSC group), and 1×105 huMSCs (MSC group), respectively, in a total of 54 mice (n = 18 each). Hind limb motor function was evaluated in open-field tests using the Basso Mouse Scale (BMS) at days post-operation (dpo) 1, 3, 5 and 7 after spinal cord injury, and weekly thereafter. Spinal cord and serum samples were harvested at dpo 7, 14 and 21. HE staining and Masson staining were used to evaluate the morphological changes and fibrosis area. The differentiation of the transplanted cells in vivo was evaluated with immunohistochemical staining. Results: The hiPSC-NSC-treated group presented a significantly smaller GFAP+ area than MSC-treated mice at all time points. Additionally, MSC-transplanted mice had a similar GFAP+ area to mice receiving PBS. At dpo14, the immunostained hiPSC-NSCs were positive for SOX2. Furthermore, the transplanted hiPSC-NSCs differentiated into glial fibrillary acidic protein (GFAP)-positive astrocytes and beta-III tubulin-positive neurons, whereas the transplanted huMSCs differentiated into GFAP-positive astrocytes. In addition, hiPSC-NSC transplantation reduced fibrosis formation and the inflammation level. Compared with the control or huMSC transplanted group, the group with transplantation of hiPSC-NSCs exhibited significantly improved behaviours, particularly limb coordination. Conclusions: HiPSC-NSCs promote functional recovery in mice with acute SCI by replacing missing neurons and attenuating fibrosis, glial scar formation, and inflammation.

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Section: Discussionmentioning

confidence: 99%

HiPSC-Derived NSCs Effectively Promote The Functional Recovery of Acute Spinal Cord Injury in Mice

Kong

Feng

Asiamah

et al. 2020

Preprint

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“…Neural stem cells (NSCs) are self-renewing multipotent cells with the capacity to differentiate into neurons and glial cells (astrocytes and oligodendrocytes) (Pollard et al, 2006b;Conti and Cattaneo, 2010). The use of NSCs combined with engineered biomaterials has the potential to provide new therapeutic routes, including the regeneration of the central nervous system (CNS) when impaired by neurodegenerative diseases, such as Alzheimer or Parkinson diseases, or traumatic injuries such as spinal cord injury (Grochowski et al, 2018;Pereira et al, 2019). Moreover, NSCs can be used to generate in vitro disease models (Jakel et al, 2004;Zhao and Moore, 2018), which may be important tools to provide new insights into disease mechanisms, as well as to discover and test new drugs (Gorba and Conti, 2013).…”

Section: Introductionmentioning

confidence: 99%

Functionalization of Electrospun Nanofibers and Fiber Alignment Enhance Neural Stem Cell Proliferation and Neuronal Differentiation

Sousa

Rodrigues

Ferreira

et al. 2020

Front. Bioeng. Biotechnol.

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Neural stem cells (NSCs) have the potential to generate the cells of the nervous system and, when cultured on nanofiber scaffolds, constitute a promising approach for neural tissue engineering. In this work, the impact of combining nanofiber alignment with functionalization of the electrospun poly-ε-caprolactone (PCL) nanofibers with biological adhesion motifs on the culture of an NSC line (CGR8-NS) is evaluated. A five-rank scale for fiber density was introduced, and a 4.5 level, corresponding to 70-80% fiber density, was selected for NSC in vitro culture. Aligned nanofibers directed NSC distribution and, especially in the presence of laminin (PCL-LN) and the RGD-containing peptide GRGDSP (PCL-RGD), promoted higher cell elongation, quantified by the eccentricity and axis ratio. In situ differentiation resulted in relatively higher percentage of cells expressing Tuj1 in PCL-LN, as well as significantly longer neurite development (41.1 ± 1.0 µm) than PCL-RGD (32.0 ± 1.0 µm), pristine PCL (25.1 ± 1.2 µm), or PCL-RGD randomly oriented fibers (26.5 ± 1.4 µm), suggesting that the presence of LN enhances neuronal differentiation. This study demonstrates that aligned nanofibers, functionalized with RGD, perform as well as PCL-LN fibers in terms of cell adhesion and proliferation. The presence of the full LN protein improves neuronal differentiation outcomes, which may be important for the use of this system in tissue engineering applications.

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“…At later time points, a glial/fibrotic scar forms and provides a barrier that prevents axonal regeneration (Tran, Warren, & Silver, ). Current regenerative therapies in SCI include delivery of exogenous stem cells (Pereira, Marote, Salgado, & Silva, ) and/or the incorporation of biomolecular scaffolds into the damaged spinal cord (Kim, Park, & Choi, ). However, regenerative failure remains a consistent feature of SCI in animal models and humans.…”

Section: Introductionmentioning

confidence: 99%

Molecular and histologic outcomes following spinal cord injury in spiny mice, Acomys cahirinus

Streeter

Sunshine

Brant

et al. 2019

J of Comparative Neurology

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The spiny mouse (Acomys cahirinus) appears to be unique among mammals by showing little scarring or fibrosis after skin or muscle injury, but the Acomys response to spinal cord injury (SCI) is unknown. We tested the hypothesis that Acomys would have molecular and immunohistochemical evidence of reduced spinal inflammation and fibrosis following SCI as compared to C57BL/6 mice (Mus), which similar to all mammals studied to date exhibits spinal scarring following SCI. Initial experiments used two pathway-focused RT-PCR gene arrays ("wound healing" and "neurogenesis") to evaluate tissue samples from the C2-C6 spinal cord 3 days after a C3/C4 hemi-crush injury (C3Hc). Based on the gene array results, specific genes were selected for RT-qPCR evaluation using species-specific primers. The results supported our hypothesis by showing increased inflammation and fibrosis related gene expression (Serpine 1, Plau, and Timp1) in Mus as compared to Acomys (p < .05).RT-qPCR also showed enhanced stem cell and axonal guidance related gene expression (Bmp2, GDNF, and Shh) in Acomys compared to Mus (p < .05). Immunohistochemical evaluation of the spinal lesion at 4 weeks postinjury indicated less collagen IV immunostaining in Acomys (p < .05). Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1(IBA1) immunostaining indicated morphological differences in the appearance of astrocytes and macrophages/microglia in Acomys.Collectively, the molecular and histologic results support the hypothesis that Acomys has reduced spinal inflammation and fibrosis following SCI. We suggest that Acomys may be a useful comparative model to study adaptive responses to SCI.

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Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury

Cited by 73 publications

References 185 publications

HiPSC-Derived NSCs Effectively Promote The Functional Recovery of Acute Spinal Cord Injury in Mice

HiPSC-Derived NSCs Effectively Promote The Functional Recovery of Acute Spinal Cord Injury in Mice

Functionalization of Electrospun Nanofibers and Fiber Alignment Enhance Neural Stem Cell Proliferation and Neuronal Differentiation

Molecular and histologic outcomes following spinal cord injury in spiny mice, Acomys cahirinus

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