Metabolic Brain Disease

, Volume 32, Issue 1, pp 185–193 | Cite as

Retinoic acid-pretreated Wharton’s jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury

  • Fatemeh Sabbaghziarani
  • Keywan Mortezaee
  • Mohammad Akbari
  • Iraj Ragerdi kashani
  • Mansooreh Soleimani
  • Ashraf Moini
  • Nahid Ataeinejad
  • Adib Zendedel
  • Gholamreza Hassanzadeh
Original Article


Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton’s jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.


Wharton’s jelly mesenchymal stem cells Neurogenesis Ischemia Retinoic acid Triiodothyronine 



subventricular zone


retinoic acid


Wharton’s jelly mesenchymal stem cells


middle cerebral artery occlusion




retinoid X receptor β


brain-derived neurotrophic factor


tumor necrosis factor-α





This work was supported by the Tehran University of Medical Sciences [grant number 93-02-30-25143].

Compliance with ethical standards

Conflict of interest

The authors disclose no potential conflicts of interest to declare


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Fatemeh Sabbaghziarani
    • 1
  • Keywan Mortezaee
    • 2
  • Mohammad Akbari
    • 1
  • Iraj Ragerdi kashani
    • 1
  • Mansooreh Soleimani
    • 3
  • Ashraf Moini
    • 4
  • Nahid Ataeinejad
    • 1
  • Adib Zendedel
    • 5
  • Gholamreza Hassanzadeh
    • 1
  1. 1.Department of Anatomy, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of Anatomy, School of MedicineKurdistan University of Medical SciencesSanandajIran
  3. 3.Department of Anatomy, School of MedicineIran University of Medical SciencesTehranIran
  4. 4.Department of Gynecology and Obstetrics, Roointan Arash women’s Health Research and Education HospitalTehran University of Medical SciencesTehranIran
  5. 5.Institute of NeuroanatomyRWTH Aachen UniversityAachenGermany

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