Skip to main content

Advertisement

Log in

Study of the influence of NGF-β gene overexpression in human mesenchymal stem cells on the expression level of SOX1 and neural pathway genes

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Nerve growth factor (NGF) is a protein exhibiting an influence on the neural development and also, its’ impact on the stem cells remains a great potential treatment strategy. The influence of its overexpression on the neural pathway differentiation on Wharton’s Jelly derived MSC (WJ-MSC) has not been studied so far, but considering the fact that these cells are relatively easy to obtain, using them may indicate an innovative change in stem cell therapies. The aim of this study was to evaluate the effect of NGF overexpression in human mesenchymal stem cells (MSC) on SOX1 and genes related to the neural pathway.

Methods and results

The lentiviral transduction was performed in order to obtain the NGF overexpression, as well as RT-PCR to evaluate the expression level SOX1, SOX2, NES, NGF under influence of overexpressed NGF protein in WJ-MSC. During the study we have observed a decrease in SOX1 expression as the marker of neural stem cells. Other than that an increase of SOX2, NES and NGF was noticed, as they all are markers of early-neural as well as already differentiated neural cells. The results show a great potential of using those examined genes’ expression as a form of a new stem cell therapy.

Conclusions

The achieved overexpression of NGF in this study, led the modified MSC onto the neural pathway as well as caused a decrease of SOX1 expression and an increase of expression of genes related to neural differentiated cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Mushahary D, Spittler A, Kasper C, Weber V, Charwat V (2018) Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 93(1):19–31. doi:https://doi.org/10.1002/cyto.a.23242[Pubmed]

    Article  CAS  PubMed  Google Scholar 

  2. Li T, Xia M, Gao Y, Chen Y, Xu Y (2015) Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy. Expert Opin Biol Ther 15(9):1293–1306. https://doi.org/10.1517/14712598.2015.1051528[PubMed]

    Article  CAS  PubMed  Google Scholar 

  3. Ding DC, Chang YH, Shyu WC, Lin SZ (2015) Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transpl 24(3):339–347. https://doi.org/10.3727/096368915X686841[PubMed]

    Article  Google Scholar 

  4. Murphy MB, Moncivais K, Caplan AI (2013) Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med 45(11):e54 Published 2013 Nov 15. https://doi.org/10.1038/emm.2013.94. [PubMed].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Almalki SG, Agrawal DK (2016) Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation 92(1–2):41–51. https://doi.org/10.1016/j.diff.2016.02.005[NCBI]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Abdelmawgoud H, Saleh A (2018) Anti-inflammatory and antioxidant effects of mesenchymal and hematopoietic stem cells in a rheumatoid arthritis rat model. Adv Clin Exp Med 27(7):873–880. https://doi.org/10.17219/acem/73720[PubMed]

    Article  PubMed  Google Scholar 

  7. Song N, Scholtemeijer M, Shah K (2020) Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential. Trends Pharmacol Sci 41(9):653–664. doi:https://doi.org/10.1016/j.tips.2020.06.009[Pubmed]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jiang W, Xu J (2020) Immune modulation by mesenchymal stem cells. Cell Prolif 53(1):e12712. https://doi.org/10.1111/cpr.12712[PubMed]

    Article  PubMed  Google Scholar 

  9. Reza-Zaldivar EE, Hernández-Sapiéns MA, Minjarez B, Gutiérrez-Mercado YK, Márquez-Aguirre AL, Canales-Aguirre AA (2018) Potential Effects of MSC-Derived Exosomes in Neuroplasticity in Alzheimer’s Disease. Front Cell Neurosci 12:317 Published 2018 Sep 24. https://doi.org/10.3389/fncel.2018.00317. [PubMed].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rocco ML, Soligo M, Manni L, Aloe L (2018) Nerve Growth Factor: Early Studies and Recent Clinical Trials. Curr Neuropharmacol 16(10):1455–1465. https://doi.org/10.2174/1570159X16666180412092859[PubMed]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Aarão TLS, de Sousa JR, Falcão ASC, Falcão LFM, Quaresma JAS (2018) Nerve Growth Factor and Pathogenesis of Leprosy: Review and Update. Front Immunol 9:939 Published 2018 May 7. https://doi.org/10.3389/fimmu.2018.00939. [PubMed].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chou FC, Sytwu HK (2009) Overexpression of thioredoxin in islets transduced by a lentiviral vector prolongs graft survival in autoimmune diabetic NOD mice. J Biomed Sci. ;16(1):71. Published 2009 Aug 12. doi:https://doi.org/10.1186/1423-0127-16-71 [Pubmed]

  13. Laudet SWislet-GendebienE, Neirinckx V, Rogister B (2012) “Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?“, BioMed Research International, vol. Article ID 601560, 10 pages, 2012. https://doi.org/10.1155/2012/601560 [Hindawi]

  14. Ahmad A, Strohbuecker S, Tufarelli C, Sottile V (2017) Expression of a SOX1 overlapping transcript in neural differentiation and cancer models. Cell Mol Life Sci 74(22):4245–4258. doi:https://doi.org/10.1007/s00018-017-2580-3[Pubmed]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu X, Fang Z, Wen J et al (2020) SOX1 Is Required for the Specification of Rostral Hindbrain Neural Progenitor Cells from Human Embryonic Stem Cells [published online ahead of print, 2020 Aug 20]. iScience 23(9):101475. https://doi.org/10.1016/j.isci.2020.101475[NCBI]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang S, Cui W (2014) Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J Stem Cells 6(3):305–311. https://doi.org/10.4252/wjsc.v6.i3.305[Pubmed]

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wang Z, Oron E, Nelson B, Razis S, Ivanova N (2012) Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells. Cell Stem Cell 10(4):440–454. https://doi.org/10.1016/j.stem.2012.02.016[Pubmed]

    Article  CAS  PubMed  Google Scholar 

  18. Thomson E, Dawson R, H’ng CH, Adikusuma F, Piltz S, Thomas PQ (2021) The Nestin neural enhancer is essential for normal levels of endogenous Nestin in neuroprogenitors but is not required for embryo development. PLoS ONE 16(11):e0258538 Published 2021 Nov 5. doi:https://doi.org/10.1371/journal.pone.0258538. [Pubmed].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hendrickson ML, Rao AJ, Demerdash ON, Kalil RE (2011) Expression of nestin by neural cells in the adult rat and human brain. PLoS ONE 6(4):e18535 Published 2011 Apr 7. doi:https://doi.org/10.1371/journal.pone.0018535. [Pubmed].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhang J, Lian M, Cao P et al (2017) Effects of Nerve Growth Factor and Basic Fibroblast Growth Factor Promote Human Dental Pulp Stem Cells to Neural Differentiation. Neurochem Res 42(4):1015–1025. https://doi.org/10.1007/s11064-016-2134-3[Pubmed]

    Article  CAS  PubMed  Google Scholar 

  21. Colafrancesco V, Villoslada P (2011) Targeting NGF pathway for developing neuroprotective therapies for multiple sclerosis and other neurological diseases. Arch Ital Biol 149(2):183–192. https://doi.org/10.4449/aib.v149i2.1376[Pubmed]

    Article  PubMed  Google Scholar 

  22. Ding J, Cheng Y, Gao S, Chen J (2011) Effects of nerve growth factor and Noggin-modified bone marrow stromal cells on stroke in rats. J Neurosci Res 89(2):222–230. https://doi.org/10.1002/jnr.22535[Pubmed]

    Article  CAS  PubMed  Google Scholar 

  23. Keefe KM, Sheikh IS, Smith GM (2017) Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury. Int J Mol Sci. ;18(3):548. Published 2017 Mar 3. doi:https://doi.org/10.3390/ijms18030548 [Pubmed]

  24. Hong-Tian Z, Zhi-Liang L, Xue-Qin Y, Zhi-Jun Y, Ru-Xiang X (2020) Neural differentiation ability of mesenchymal stromal cells from bone marrow and adipose tissue: a comparative study. Cytotherapy 14(10):1203–1214. https://doi.org/10.3109/14653249.2012.711470[Researchgate]

    Article  CAS  Google Scholar 

  25. Borkowska P, Zielinska A, Paul-Samojedny M, Stojko R, Kowalski J (2020) Evaluation of reference genes for quantitative real-time PCR in Wharton’s Jelly-derived mesenchymal stem cells after lentiviral transduction and differentiation. Mol Biol Rep 47:1107–1115. https://doi.org/10.1007/s11033-019-05207-6[Pubmed]

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Authors would like to thank prof. Rafał Stojko MD, PhD for umbilical cords’ collection.

Funding

This work was supported by the Medical University of Silesia, grant number PCN-1-012/N/1/B.

Author information

Authors and Affiliations

Authors

Contributions

Study concept and design- PB; acquisition of data- JM, AZ.; analysis and interpretation of data- JM.; drafting the manuscript- JM; statistical analysis- PB, JM; technical or material support- JK; All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Julia Morys.

Ethics declarations

Conflict of interest

The authors declare no relevant interests to disclose.

Ethics approval

The Bioethical Committee of the Medical University of Silesia in Katowice (Resolution No. KNW/022/KB/195/14) confirmed its acceptance for the entire technique of conducting this exploration.

Consent to participate

The volunteering mothers were informed of the procedure details. The study begun after receiving their full, written consent.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morys, J., Borkowska, P., Zielinska, A. et al. Study of the influence of NGF-β gene overexpression in human mesenchymal stem cells on the expression level of SOX1 and neural pathway genes. Mol Biol Rep 49, 4435–4441 (2022). https://doi.org/10.1007/s11033-022-07283-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-07283-7

Keywords

Navigation