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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

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Abstract

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.

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Abbreviations

SVZ:

subventricular zone

RA:

retinoic acid

WJ-MSCs:

Wharton’s jelly mesenchymal stem cells

MCAO:

middle cerebral artery occlusion

T3:

triiodothyronine

RXRβ:

retinoid X receptor β

BDNF:

brain-derived neurotrophic factor

TNF-α:

tumor necrosis factor-α

IL-6:

interleukin-6

References

  • Casals JB, Pieri NC, Feitosa ML, Ercolin A, Roballo K, Barreto RS, et al. (2011) The use of animal models for stroke research: a review. Commun Med 61:305–313

    CAS  Google Scholar 

  • Drela K, Lech W, Figiel-Dabrowska A, Zychowicz M, Mikula M, Sarnowska A, Domanska-Janik K (2016) Enhanced neuro-therapeutic potential of Wharton’s jelly–derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture. Cytotherapy 18:497–509

    Article  CAS  PubMed  Google Scholar 

  • Dugue R, Barone FC (2016) Ischemic, traumatic and neurodegenerative brain inflammatory changes. Future Neurol 11:77–96

    Article  CAS  Google Scholar 

  • Ferri AL, Cavallaro M, Braida D, Di Cristofano A, Canta A, Vezzani A, et al. (2004) Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131:3805–3819

    Article  CAS  PubMed  Google Scholar 

  • Frausin S, Viventi S, Falzacappa LV, Quattromani MJ, Leanza G, Tommasini A, Valencic E (2015) Wharton’s jelly derived mesenchymal stromal cells: Biological properties, induction of neuronal phenotype and current applications in neurodegeneration research. Acta Histochem 117:329–338

    Article  CAS  PubMed  Google Scholar 

  • Gong M, Bi Y, Jiang W, Zhang Y, Chen L, Hou N, et al. (2013) Retinoic acid receptor beta mediates all-trans retinoic acid facilitation of mesenchymal stem cells neuronal differentiation. Int J Biochem Cell Biol 45:866–875

    Article  CAS  PubMed  Google Scholar 

  • Katsuki H, Kurimoto E, Takemori S, Kurauchi Y, Hisatsune A, Isohama Y, et al. (2009) Retinoic acid receptor stimulation protects midbrain dopaminergic neurons from inflammatory degeneration via BDNF-mediated signaling. J Neurochem 110:707–718

    Article  CAS  PubMed  Google Scholar 

  • Koh SH, Park HH (2016) Neurogenesis in Stroke Recovery. Translational stroke research. doi:10.1007/s12975–016-0460-z [Epub ahead of print]

    PubMed  Google Scholar 

  • König S, Neto VM (2002) Thyroid hormone actions on neural cells. Cell Mol Neurobiol 22:517–544

    Article  PubMed  Google Scholar 

  • Kreżel W, Kastner P, Chambon P (1999) Differential expression of retinoid receptors in the adult mouse central nervous system. Neuroscience 89:1291–1300

    Article  PubMed  Google Scholar 

  • Lee C, Hu J, Ralls S, Kitamura T, Loh YP, Yang Y, et al. (2012) The molecular profiles of neural stem cell niche in the adult subventricular zone. PLoS One 7:e50501

  • Linnarsson S, Willson CA, Ernfors P (2000) Cell death in regenerating populations of neurons in BDNF mutant mice. Mol Brain Res 75:61–69

    Article  CAS  PubMed  Google Scholar 

  • Lucassen PJ, Oomen CA, Naninck EF, Fitzsimons CP, van Dam A-M, Czeh B, Korosi A (2015) Regulation of adult neurogenesis and plasticity by (early) stress, glucocorticoids, and inflammation. Cold Spring Harb Perspect Biol 7:a021303

    Article  PubMed  Google Scholar 

  • Mano H, Mori R, Ozawa T, Takeyama K-i, Yoshizawa Y, Kojima R, et al. (1994) Positive and negative regulation of retinoid X receptor gene expression by thyroid hormone in the rat. Transcriptional and post-transcriptional controls by thyroid hormone. J Biol Chem 269:1591–1594

    CAS  PubMed  Google Scholar 

  • Mdzinarishvili A, Sutariya V, Talasila PK, Geldenhuys WJ, Sadana P (2013) Engineering triiodothyronine (T3) nanoparticle for use in ischemic brain stroke. Drug delivery and translational research 3(4):309–317

    Article  CAS  PubMed  Google Scholar 

  • Mortezaee K, Minaii B, Sabbaghziarani F, Kashani IR, Hassanzadeh G, Pasbakhsh P, et al. (2015) Retinoic acid as the stimulating factor for differentiation of Wharton’s jelly-mesenchymal stem cells into hepatocyte-like cells. Avicenna journal of medical biotechnology 7(3):106–112

    PubMed  PubMed Central  Google Scholar 

  • Núñez V, Alameda D, Rico D, Mota R, Gonzalo P, Cedenilla M, et al. (2010) Retinoid X receptor α controls innate inflammatory responses through the up-regulation of chemokine expression. Proc Natl Acad Sci 107:10626–10631

    Article  PubMed  PubMed Central  Google Scholar 

  • Pires AO, Neves-Carvalho A, Sousa N (2014) Salgado AJ (2014) The secretome of bone marrow and wharton jelly derived mesenchymal stem cells induces differentiation and neurite outgrowth in SH-SY5Y Cells. Stem Cells Int 438352

  • Straub RH (2014) Interaction of the endocrine system with inflammation: a function of energy and volume regulation. Arthritis Res Ther 16:203

  • Sui L, Ren W-W, Li B-M (2010) Administration of thyroid hormone increases reelin and brain-derived neurotrophic factor expression in rat hippocampus in vivo. Brain Res 1313:9–24

    Article  CAS  PubMed  Google Scholar 

  • Sullivan R, Duncan K, Dailey T, Kaneko Y, Tajiri N, Borlongan CV (2015) A possible new focus for stroke treatment–migrating stem cells. Expert Opin Biol Ther 15:949–958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tovar-y-Romo LB, Penagos-Puig A, Ramírez-Jarquín JO (2016) Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate. J Neurochem 136:13–27

    Article  CAS  PubMed  Google Scholar 

  • Wang T-W, Zhang H, Parent JM (2005) Retinoic acid regulates postnatal neurogenesis in the murine subventricular zone-olfactory bulb pathway. Development 132:2721–2732

    Article  CAS  PubMed  Google Scholar 

  • Zendedel A, Habib P, Dang J, Lammerding L, Hoffmann S, Beyer C, Slowik A (2015) Omega-3 polyunsaturated fatty acids ameliorate neuroinflammation and mitigate ischemic stroke damage through interactions with astrocytes and microglia. J Neuroimmunol 278:200–211

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran

    Fatemeh Sabbaghziarani, Mohammad Akbari, Iraj Ragerdi kashani, Nahid Ataeinejad & Gholamreza Hassanzadeh

  2. Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Keywan Mortezaee

  3. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mansooreh Soleimani

  4. Department of Gynecology and Obstetrics, Roointan Arash women’s Health Research and Education Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Ashraf Moini

  5. Institute of Neuroanatomy, RWTH Aachen University, 52074, Aachen, Germany

    Adib Zendedel

Authors
  1. Fatemeh Sabbaghziarani
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  2. Keywan Mortezaee
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  3. Mohammad Akbari
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  4. Iraj Ragerdi kashani
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  5. Mansooreh Soleimani
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  6. Ashraf Moini
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  7. Nahid Ataeinejad
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  8. Adib Zendedel
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  9. Gholamreza Hassanzadeh
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Correspondence to Gholamreza Hassanzadeh.

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Sabbaghziarani, F., Mortezaee, K., Akbari, M. et al. 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. Metab Brain Dis 32, 185–193 (2017). https://doi.org/10.1007/s11011-016-9897-8

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