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Human Placental Mesenchymal Stem Cell-derived Exosomes in Combination with Hyperbaric Oxygen Synergistically Promote Recovery after Spinal Cord Injury in Rats

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Abstract

Spinal cord injury (SCI) is a critical medical condition during which sensorimotor function is lost. Current treatments are still unable to effectively improve these conditions, so it is important to pay attention to other effective approaches. Currently, we investigated the combined effects of human placenta mesenchymal stem cells (hPMSCs)-derived exosomes along with hyperbaric oxygen (HBO) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley (SD) rats were allocated into five equal groups, including; sham group, SCI group, Exo group (underwent SCI and received hPMSCs-derived exosomes), HBO group (underwent SCI and received HBO), and Exo+HBO group (underwent SCI and received hPMSCs-derived exosomes plus HBO). Tissue samples at the lesion site were obtained for the evaluation of stereological, immunohistochemical, biochemical, molecular, and behavioral characteristics. Findings showed a significant increase in stereological parameters, biochemical factors (GSH, SOD, and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in treatment groups, especially Exo+HBO group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells and gliosis, as well as expression of inflammatory genes (TNF-α and IL-1β) were considerably reduced in treatment groups, especially Exo+HBO group, compared to SCI group. We conclude that co-administration of hPMSCs-derived exosomes and HBO has synergistic neuroprotective effects in animals undergoing SCI.

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Data Availability

All the data is available with Dr. Davood Nasiry, reasonable request will be responded with supplementary raw-data.

Abbreviations

SCI:

Spinal cord injury

hPMSCs:

Human placenta mesenchymal stem cells

HBO:

Hyperbaric oxygen

SD:

Sprague-Dawley

PBS:

Phosphate-buffered saline

DMEM:

Dulbecco modified Eagle medium

TEM:

Transmission electron microscopy

PVDF:

Polyvinylidene difluoride

TBST:

Tris-buffered-saline-tween

DAB:

3,3-Diaminobenzidine

DLS:

Dynamic light scattering

IP:

Intraperitoneal

GFAP:

Glial fibrillary acidic protein

MDA:

Malondialdehyde

GSH:

Glutathione

SOD:

Superoxide dismutase

CAT:

Catalase

qRT-PCR:

Quantitative real-time polymerase chain reaction

cDNA:

Complementary DNA

IL-10:

Interleukin-10

TNF-α:

Tumor necrosis factor-alpha

IL-10:

Interleukin-1beta

BBB:

Basso-Beattie-Bresnehan

NBT:

Narrow beam walking test

EMG:

Electromyography

ANOVA:

One-way analysis of variance

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Funding

This work was supported by Mazandaran University of Medical Sciences (Grant no: 13781).

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Authors and Affiliations

  1. Department of Treatment, Iran University of Medical Sciences, Tehran, Iran

    Hosna Cheshmi

  2. Department of Bioimaging, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Hossein Mohammadi

  3. Department of Eye, Amiralmomenin Hospital, School of Medicine, Guilan University of Medical Science, Rasht, Iran

    Mitra Akbari

  4. Department of Paramedicine, Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, 4615861468, Iran

    Davood Nasiry, Mehri Mirhoseini & Hossein Mokhtari

  5. Department of Psychiatric Nursing and Management, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, 5865272565, Iran

    Rafat Rezapour-Nasrabad

  6. Department of Biological Science and Technology, Faculty of Nano and Bio Science and Technology, Persian Gulf University, Bushehr, 75169, Iran

    Mahdi Bagheri

  7. Trauma research center, Aja University of Medical Sciences, Tehran, Iran

    Beheshteh Abouhamzeh

  8. Department of Artificial Intelligence, Smart University of Medical Sciences, Tehran, Iran

    Mahnaz Poorhassan

  9. School of Medicine, Department of Physiology, Mazandaran University of Medical Sciences, Sari, Iran

    Esmaeil Akbari

  10. Cellular and Molecular research center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Amir Raoofi

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  1. Hosna Cheshmi
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  2. Hossein Mohammadi
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  3. Mitra Akbari
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  4. Davood Nasiry
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Contributions

Methodology: Davood Nasiry, Rafat Rezapour-Nasrabad, Hossein Mohammadi, Beheshteh Abouhamzeh; Formal analysis: Mahnaz Poorhassan, Mehri Mirhoseini, Hossein Mokhtari, Esmaeil Akbari, Amir Raoofi; Investigation: Hosna Cheshmi; Writing-original draft: Davood Nasiry, Beheshteh Abouhamzeh; Writing - review & editing: Davood Nasiry, Rafat Rezapour-Nasrabad, Amir Raoofi; Supervision: Davood Nasiry; Funding acquisition: Davood Nasiry.

Corresponding authors

Correspondence to Davood Nasiry or Rafat Rezapour-Nasrabad.

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Ethics approval

The use of human placenta samples was approved by the ethics committee of Mazandaran University of Medical Sciences, and written informed consent was obtained before clinical sampling. The methods were carried out in compliance with the ARRIVE guidelines. All experimental protocols were approved by Ethics Committee based on NIH Guide for the Care and Use of Laboratory Animals (Ethic no: IR.MAZUMS.4.REC.1400.13781).

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Cheshmi, H., Mohammadi, H., Akbari, M. et al. Human Placental Mesenchymal Stem Cell-derived Exosomes in Combination with Hyperbaric Oxygen Synergistically Promote Recovery after Spinal Cord Injury in Rats. Neurotox Res 41, 431–445 (2023). https://doi.org/10.1007/s12640-023-00649-0

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