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Intracerebroventricular Delivery of Human Umbilical Cord Mesenchymal Stem Cells as a Promising Therapy for Repairing the Spinal Cord Injury Induced by Kainic Acid

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Abstract

Spinal cord injury (SCI) is a common pathological condition that leads to permanent or temporal loss of motor and autonomic functions. Kainic acid (KA), an agonist of kainate receptors, a type of ionotropic glutamate receptor, is widely used to induce experimental neurodegeneration models of CNS. Mesenchymal Stem Cells (MSC) therapy applied at the injured nervous tissue have emerged as a promising therapeutic treatment. Here we used a validated SCI experimental model in which an intraparenchymal injection of KA into the C5 segment of rat spinal cord induced an excitotoxic lesion. Three days later, experimental animals were treated with an intracerebroventricular injection of human umbilical cord (hUC) MSC whereas control group only received saline solution. Sensory and motor skills as well as neuronal and glial reaction of both groups were recorded. Differences in motor behavior, neuronal counting and glial responses were observed between hUC-MSC-treated and untreated rats. According to the obtained results, we suggest that hUC-MSC therapy delivered into the fourth ventricle using the intracerebroventricular via can exert a neuroprotective or neurorestorative effect on KA-injected animals.

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Acknowledgements

This work was supported by the National Agency for Promotion of Science and Technology (ANPCyT) (grant PICT 2015-2087 to FN and PICT 2015-1998 to PCR) and by the National University of La Plata (grant V270 to ELP). The authors thank Dr. G. Mazzolini and Dr. M.G. García (Universidad Austral, CONICET) for kindly providing the hUC-MSC. The expert handling of animals by Mr. H. Enrique is gratefully acknowledged.

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Author notes

  1. Authors Nishida and Zappa Villar contributed equally to this study. Senior authors Reggiani and Portiansky contributed equally to this study.

Authors and Affiliations

  1. Image Analysis Laboratory, School of Veterinary Sciences, National University of La Plata (UNLP), Calles 60 y 118, 1900, La Plata, Buenos Aires, Argentina

    Fabián Nishida, Carolina N. Zanuzzi, María S. Sisti, Agustina E. Camiña & Enrique L. Portiansky

  2. National Research Council of Science and Technology (CONICET), Buenos Aires, Argentina

    Fabián Nishida, María F. Zappa Villar, Carolina N. Zanuzzi, María S. Sisti, Paula C. Reggiani & Enrique L. Portiansky

  3. INIBIOLP, School of Medical Sciences, UNLP, La Plata, Buenos Aires, Argentina

    María F. Zappa Villar & Paula C. Reggiani

  4. Department of Histology and of Embryology B, School of Medical Sciences, UNLP, La Plata, Buenos Aires, Argentina

    María F. Zappa Villar & Paula C. Reggiani

  5. Department of Histology and Embryology, School of Veterinary Sciences, UNLP, La Plata, Buenos Aires, Argentina

    Carolina N. Zanuzzi

Authors
  1. Fabián Nishida
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  2. María F. Zappa Villar
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  3. Carolina N. Zanuzzi
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  4. María S. Sisti
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  5. Agustina E. Camiña
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  6. Paula C. Reggiani
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  7. Enrique L. Portiansky
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Corresponding author

Correspondence to Carolina N. Zanuzzi.

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The authors do not have any financial conflict of interests to disclose.

Research Involving Animals

All experiments with animals were performed according to the recommendations of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was also approved by the School of Veterinary Sciences, National University of Plata Institutional Committee for Care and Use of Laboratory Animals (CICUAL), code n° 49-8-15 P.

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Nishida, F., Zappa Villar, M.F., Zanuzzi, C.N. et al. Intracerebroventricular Delivery of Human Umbilical Cord Mesenchymal Stem Cells as a Promising Therapy for Repairing the Spinal Cord Injury Induced by Kainic Acid. Stem Cell Rev and Rep 16, 167–180 (2020). https://doi.org/10.1007/s12015-019-09934-y

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  • DOI: https://doi.org/10.1007/s12015-019-09934-y

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