Modeling traumatic injury in organotypic spinal cord slice culture obtained from adult rat

Pandamooz, Sareh; Salehi, Mohammad Saied; Zibaii, Mohammad Ismail; Safari, Anahid; Nabiuni, Mohammad; Ahmadiani, Abolhassan; Dargahi, Leila

doi:10.1016/j.tice.2019.01.002

Cited by 17 publications

(16 citation statements)

References 48 publications

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“…One ex vivo human spinal cord schwannoma culture [ 45 ], one postmortem human spinal cord model derived from adult autopsy tissue [ 46 ], and one human fetal spinal cord tissue culture [ 47 ]. However, different from these previous reports, the human slice culture method utilized in the present study is an interface-based method (modified from the method by Stoppini et al [ 13 ] and Bonnici and Kapfhammer [ 48 ]) that retained relatively intact anatomical structure, local circuitry, glial/neuronal interactions, and viability similar to that reported in cultures of rodent origin [ 23 , 49 – 51 ].…”

Section: Discussionmentioning

confidence: 93%

Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy

et al. 2020

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Background: There are multiple promising treatment strategies for central nervous system trauma and disease. However, to develop clinically potent and safe treatments, models of human-specific conditions are needed to complement in vitro and in vivo animal model-based studies. Methods: We established human brain stem and spinal cord (cross-and longitudinal sections) organotypic cultures (hOCs) from first trimester tissues after informed consent by donor and ethical approval by the Regional Human Ethics Committee, Stockholm (lately referred to as Swedish Ethical Review Authority), and The National Board of Health and Welfare, Sweden. We evaluated the stability of hOCs with a semi-quantitative hOC score, immunohistochemistry, flow cytometry, Ca 2+ signaling, and electrophysiological analysis. We also applied experimental allogeneic human neural cell therapy after injury in the ex vivo spinal cord slices. Results: The spinal cord hOCs presented relatively stable features during 7-21 days in vitro (DIV) (except a slightly increased cell proliferation and activated glial response). After contusion injury performed at 7 DIV, a significant reduction of the hOC score, increase of the activated caspase-3 + cell population, and activated microglial populations at 14 days postinjury compared to sham controls were observed. Such elevation in the activated caspase-3 + population and activated microglial population was not observed after allogeneic human neural cell therapy. Conclusions: We conclude that human spinal cord slice cultures have potential for future structural and functional studies of human spinal cord development, injury, and treatment strategies.

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Section: Discussionmentioning

confidence: 93%

Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy

et al. 2020

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“…Unfortunately, animal studies offer complexity, which is very difficult to model in vitro, and high variability, which prevents reproducible studies 88,89 . For this reason, organotypic cultures of spinal cord explants could be an option to obtain reproducible results after a contusion injury 87,90 . The spinal cord explants are cut to obtain slices, called organotypic slices (OTSs), that preserve the basic structural and connective organization of their original tissue (organotypic).…”

Section: Severe Contusion Model As the New Gold Standard: How?mentioning

confidence: 99%

“…The OTS-SC model is suitable for axonal growth evaluation because the typical ventrodorsal polarity of the SC is maintained after a culture period of 2 weeks, and intrinsic spinal cord axons formed a strong fiber tract extending along the longitudinal axis of the slice 87,90 (Figure 9). A well defined in vitro evaluation could contribute to understanding the results of in vivo analysis, for example, Basso, Beattie, and Bresnahan locomotor score (BBB), ladder climbing test, electrophysiological recordings such as the rate-dependent depression (RDD) of the Hoffmann's reflex (H-reflex), defined as "the decrease in reflex magnitude relative to repetition rate" 3 , suitable for evaluating sensorimotor improvements and spasticity.…”

Section: Severe Contusion Model As the New Gold Standard: How?mentioning

confidence: 99%

Injectable Scaffold-Systems for the Regeneration of Spinal Cord: Advances of the Past Decade

Santi

Corridori

Pugno

et al. 2021

ACS Biomater. Sci. Eng.

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Nowadays, whenever is possible and as alternative to open spine surgery, minimally invasive procedures are preferred to treat spinal cord injuries (SCI), with percutaneous injections or small incisions, that are faster, less traumatic and require less recovery time. Injectable repair systems are based on materials that can be injected in the lesion site, can eventually be loaded with drugs or even cells, and act as scaffolds for the lesion repair. The review analyzed papers written from 2010 onwards on injectable materials/systems used/proposed for the regenerative and combinatorial therapies of SCI, and discusses the in vivo models that have been used to validate them.

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“…Based on the above presented studies, BM-MSCs and neural stem cells are the most abundantly used cell-types that can be genetically modified to enhance their potential when transplanted in animal models of stroke. However, our investigations revealed that epidermal neural crest stem cells (EPI-NCSCs) can also benefit the inhospitable context of rat model of ischemic stroke [34] as well as ex vivo [114] and in vivo [115] models of spinal cord injury. EPI-NCSCs are located in the bulge area of the hair follicle, and retain the differentiation potential of their neural crest origin, so that they can differentiate into neural lineages [116].…”

Section: Epidermal Neural Crest Stem Cells As a Promising Candidate Imentioning

confidence: 99%

The Beneficial Potential of Genetically Modified Stem Cells in the Treatment of Stroke: A Review

Salehi¹,

Safari²,

Pandamooz³

et al. 2020

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The last two decades have witnessed a surge in investigations proposing stem cells as a promising strategy to treat stroke. Since growth factor release is considered as one of the most important aspects of cell-based therapy, stem cells over-expressing growth factors are hypothesized to yield higher levels of therapeutic efficiency. In pre-clinical studies of the last 15 years that were investigating the efficiency of stem cell therapy for stroke, a variety of stem cell types were genetically modified to over-express various factors. In this review we summarize the current knowledge on the therapeutic efficiency of stem cell-derived growth factors, encompassing techniques employed and time points to evaluate. In addition, we discuss several types of stem cells, including the recently developed model of epidermal neural crest stem cells, and genetically modified stem cells over-expressing specific factors, which could elevate the restorative potential of naive stem cells. The restorative potential is based on enhanced survival/differentiation potential of transplanted cells, apoptosis inhibition, infarct volume reduction, neovascularization or functional improvement. Since the majority of studies have focused on the short-term curative effects of genetically engineered stem cells, we emphasize the need to address their long-term impact.

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Modeling traumatic injury in organotypic spinal cord slice culture obtained from adult rat

Cited by 17 publications

References 48 publications

Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy

Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy

Injectable Scaffold-Systems for the Regeneration of Spinal Cord: Advances of the Past Decade

The Beneficial Potential of Genetically Modified Stem Cells in the Treatment of Stroke: A Review

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