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Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model

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Abstract

Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSCFGF1) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 106 AD-MSCFGF1 was administrated intravenously 30 min after carotid reperfusion. The ability of technetium99m-hexamethyl propylene amine oxime (99mTc-HMPAO)-labeled AD-MSCFGF1 to enter into ischemic brain was evaluated 2 h post injection. 24 h post operation, the neurological recovery (rotarod and Roger’s tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The 99mTc-HMPAO-labeled AD-MSCFGF1 could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSCFGF1 resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSCFGF1 can be a novel and promising candidate approach for the treatment of ischemic stroke.

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Acknowledgements

This work was supported by the Vice Chancellery for Research and Technology and the Stem Cell Research and Application Core of Mashhad University of Medical Sciences grants (921716) and by the Iran’s Vice-Presidency for Science and Technology grant (11/63941).

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Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamed Ghazavi, Seyed Javad Hoseini & Elahe Mahdipour

  2. Department of Anatomy and Cell Biology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Alireza Ebrahimzadeh-Bideskan

  3. Department of Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Baratali Mashkani

  4. Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Soghra Mehri

  5. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

    Ahmad Ghorbani & Azar Hoseini

  6. Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Kayvan Sadri

  7. Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

    Faezeh Ghasemi

  8. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Forouzanfar & Hamid Reza Sadeghnia

  9. Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Ali Reza Pasdar, Hamid Reza Sadeghnia & Majid Ghayour-Mobarhan

  10. Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, 99199-91766, Iran

    Hamid Reza Sadeghnia

  11. Biochemistry of Nutrition Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 99199-91766, Iran

    Majid Ghayour-Mobarhan

  12. Cardiovascular Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Majid Ghayour-Mobarhan

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  1. Hamed Ghazavi
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  2. Seyed Javad Hoseini
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  9. Faezeh Ghasemi
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  10. Fatemeh Forouzanfar
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  12. Ali Reza Pasdar
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  13. Hamid Reza Sadeghnia
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  14. Majid Ghayour-Mobarhan
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Correspondence to Hamid Reza Sadeghnia or Majid Ghayour-Mobarhan.

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Ghazavi, H., Hoseini, S.J., Ebrahimzadeh-Bideskan, A. et al. Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model. Stem Cell Rev and Rep 13, 670–685 (2017). https://doi.org/10.1007/s12015-017-9755-z

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