Hypoxic Preconditioning Increases the Neuroprotective Effects of Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury

Imura, Takeshi; Tomiyasu, Mayumi; Otsuru, Naofumi; Nakagawa, Kei; Otsuka, Takashi; Takahashi, Shinya; Takeda, Masaaki; Shrestha, Looniva; Kawahara, Yumi; Fukazawa, Takahiro; Sueda, Taijiro; Tanimoto, Keiji; Yuge, Louis

doi:10.4172/2157-7633.1000375

Cited by 11 publications

(8 citation statements)

References 54 publications

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“…Cell death via necrosis and necroptosis is involved in the formation of cavities in the injured spinal cord tissue 26 . The effect of transplanting MSCs derived from bone marrow and adipose tissue on these inflammatory cytokines has also been reported in SCI models 21 , 27 , 28 . In contrast, the effect of transplanting MSCs derived from cranial bone into an SCI model has not been reported.…”

Section: Discussionmentioning

confidence: 93%

“…Previous studies have shown that both IL-1β and TNF-α are upregulated after nerve injury 19 , 20 . In addition, the expressions of pro-inflammatory cytokines, such as TNF-α and IL-1β, increased after SCI 20 , 21 . These cytokines induce an inflammatory response, increase vascular permeability, elevate the levels of reactive oxygen species, and finally cause cell death via apoptosis and necroptosis 22 – 24 .…”

Section: Discussionmentioning

confidence: 97%

“…NG108-15 cells were exposed to oxidative and inflammatory stress to evaluate the neuroprotective effects of rbMSCs and rcMSCs, as previously described 7 . H 2 O 2 (Santoku Chemical Industries, Tokyo, Japan) was used to mimic oxidative stimulus, and lipopolysaccharides (LPS) (Wako Pure Chemical Industries) were used to mimic inflammatory stimulus 21 , 32 , 52 , 53 . NG108-15 cells were seeded on culture dishes (Sumitomo Bakelite Co.), and the medium was changed to rbMSC-CM, rcMSC-CM, and control-CM (with 500 mM H 2 O 2 or 200 ng/mL LPS).…”

Section: Methodsmentioning

confidence: 99%

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Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury

Maeda

Otsuka

Takeda

et al. 2021

Sci Rep

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Cell-based therapy using mesenchymal stem cells (MSCs) is a novel treatment strategy for spinal cord injury (SCI). MSCs can be isolated from various tissues, and their characteristics vary based on the source. However, reports demonstrating the effect of transplanted rat cranial bone-derived MSCs (rcMSCs) on rat SCI models are lacking. In this study, we determined the effect of transplanting rcMSCs in rat SCI models. MSCs were established from collected bone marrow and cranial bones. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 24 h post SCI. The recovery of motor function and hindlimb electrophysiology was evaluated 4 weeks post transplantation. Electrophysiological recovery was evaluated by recording the transcranial electrical stimulation motor-evoked potentials. Tissue repair after SCI was assessed by calculating the cavity ratio. The expression of genes involved in the inflammatory response and cell death in the spinal cord tissue was assessed by real-time polymerase chain reaction. The transplantation of rcMSCs improved motor function and electrophysiology recovery, and reduced cavity ratio. The expression of proinflammatory cytokines was suppressed in the spinal cord tissues of the rats that received rcMSCs. These results demonstrate the efficacy of rcMSCs as cell-based therapy for SCI.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

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Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury

Maeda

Otsuka

Takeda

et al. 2021

Sci Rep

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“…To analyze the neural cell viability after ischemic damage in vitro, neuroblastoma × glioma hybrid cells (NG108-15; ECACC, Porton Down, UK) were exposed to a mimic of oxidative stress created using H 2 O 2 (SANTOKU CHEMICAL INDUSTRIES Co., Ltd., Tokyo, Japan) and a mimic of inflammatory stress created using lipopolysaccharide (LPS) (Wako Pure Chemical Industries, Ltd., Osaka, Osaka, Japan) as an in vitro cerebral infarction model. 24,[30][31][32][33] NG108-15 cells were seeded into 60-mm culture dishes (Corning Inc., Corning, NY, USA) and cultured in DMEM with high-glucose (Sigma-Aldrich Co.), 10% FBS (Thermo Fisher Scientific), penicillin (100 units/ mL), streptomycin (100 µg/mL: both from Sigma-Aldrich Co.), and HAT supplement (Thermo Fisher Scientific). The culture dishes were incubated at 37°C in a humidified atmosphere with 5% CO 2 .…”

Section: Oxidative or Inflammatory Stress Exposure And Cell Death Assay On Ng108-15 Cellsmentioning

confidence: 99%

Early Transplantation of Human Cranial Bone-derived Mesenchymal Stem Cells Enhances Functional Recovery in Ischemic Stroke Model Rats

Oshita

Okazaki

Mitsuhara

et al. 2020

Neurol. Med. Chir.(Tokyo)

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We analyzed the cell characteristics, neuroprotective, and transplantation effects of human cranial bonederived mesenchymal stem cells (hcMSCs) in ischemic stroke model rats compared with human iliac bone-derived mesenchymal stem cells (hiMSCs). The expressions of brain-derived neurotrophic factor (BDNF ) and vascular endothelial growth factor (VEGF ) as neurotrophic factors were analyzed in both MSCs. hiMSCs or hcMSCs were intravenously administered into ischemic stroke model rats at 3 or 24 h after middle cerebral artery occlusion (MCAO) and neurological function was evaluated. The survival rate of neuroblastoma × glioma hybrid cells (NG108-15) after 3 or 24 h oxidative or inflammatory stress and the neuroprotective effects of hiMSCs or hcMSCs-conditioned medium (CM) on 3 or 24 h oxidative or inflammatory stress-exposed NG108-15 cells were analyzed. The expressions of BDNF and VEGF were higher in hcMSCs than in hiMSCs. hcMSCs transplantation at 3 h after MCAO resulted in significant functional recovery compared with that in the hiMSCs or control group. The survival rate of stress-exposed NG108-15 was lower after 24 h stress than after 3 h stress. The survival rates of NG108-15 cells cultured with hcMSCs-CM after 3 h oxidative or inflammatory stress were significantly higher than in the control group. Our results suggest that hcMSCs transplantation in the early stage of ischemic stroke suppresses the damage of residual nerve cells and leads to functional recovery through the strong expressions of neurotrophic factors. This is the first report demonstrating a functional recovery effect after ischemic stroke following hcMSCs transplantation.

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“…In addition, the clinical application of induced pluripotent stem cells has been planned to start within a few years [13]. The important factors in the culture process for improving cell function and therapeutic effects are considered to be cell source (cell selection) [14], [15] and culture environment such as soluble factors [16], [17], scaffolds [18], [19], [20], hypoxia [21], electrical stimulation [22], and gravity [23], [24].…”

Section: Introductionmentioning

confidence: 99%

“Microgravity” as a unique and useful stem cell culture environment for cell-based therapy

Imura

Otsuka

Kawahara³

et al. 2019

Regenerative Therapy

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Cell-based therapy using mesenchymal stem cells or pluripotent stem cells such as induced pluripotent stem cells has seen dramatic progress in recent years. Part of cell-based therapy are already covered by public medical insurance. Recently, researchers have attempted to improve therapeutic effects toward various diseases by cell transplantation. Culture environment is considered to be one of the most important factors affecting therapeutic effects, in particular factors such as physical stimuli, because cells have the potential to adapt to their surrounding environment. In this review, we provide an overview of the research on the effects of gravity alteration on cell kinetics such as proliferation or differentiation and on potential therapeutic effects, and we also summarize the remarkable possibilities of the use of microgravity culture in cell-based therapy for various diseases.

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Hypoxic Preconditioning Increases the Neuroprotective Effects of Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury

Cited by 11 publications

References 54 publications

Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury

Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury

Early Transplantation of Human Cranial Bone-derived Mesenchymal Stem Cells Enhances Functional Recovery in Ischemic Stroke Model Rats

“Microgravity” as a unique and useful stem cell culture environment for cell-based therapy

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