Investigating the Effect of Human Adipose Stem Cell-Derived Exosomes on Survival and Neural Differentiation of PC12 Cells

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Mesenchymal stem cells can be differentiated into multiple cell lineages, and secrete different factors. These secretions contain molecules and extracellular vesicles that have some effects. Exosomes are nanovesicles that enter protein and genetic material to target cells, and thereby induce proliferation, survival, and neural differentiation in target cells. So, exosomes can be considered as an ideal source for non-cellular therapy. The aim of this study was to investigate the effects of human adipose stem cell (ASC)-derived exosomes on survival and neural differentiation of pheochromocytoma cell line (PC12).Methods: The adipose tissue samples were obtained from young donors after signing the consent. The stem cells were isolated and cultured. Then exosomes were isolated from supernatant. In order to neural differentiation, the PC12 cells were treated in four groups with exosomes, nerve growth factor (NGF), NGF/exosome, and control for 7 days. The cells survival was assayed using MTT assay and neural differentiation of cells was confirmed by real-time polymerase chain reaction (real-time PCR).Findings: Based on MTT assay, there was significant difference in cell survival between exosome-treated group and other groups at days 1, 3, and 7. The results of real-time PCR showed that the expression of neural marker microtubule-associated protein 2 (Map2) significantly increased in exosome-treated group compared to other group at day 7 (P < 0.001).Conclusion: This study revealed that ASC-derived exosomes improved the survival and neural differentiation of PC12 cells. Our results suggest that exosomes may pave the way for non-cellular treatment of neurodegenerative diseases.

Keywords

References

  1. Kim SU, de Vellis J.. Stem cell-based cell therapy in neurological diseases: a review. J Neurosci Res 2009; 87(10): 2183-200.
  2. Salehi H, Amirpour N, Niapour A, Razavi S. An overview of neural differentiation potential of human adipose derived stem cells. Stem Cell Rev 2016; 12(1): 26-41.
  3. Farinazzo A, Turano E, Marconi S, Bistaffa E, Bazzoli E, Bonetti B. Murine adipose-derived mesenchymal stromal cell vesicles: in vitro clues for neuroprotective and neuroregenerative approaches. Cytotherapy 2015; 17(5): 571-8.
  4. Ishii S, Okada Y, Kadoya T, Matsuzaki Y, Shimazaki T, Okano H. Stromal cell-secreted factors promote the survival of embryonic stem cell-derived early neural stem/progenitor cells via the activation of MAPK and PI3K-Akt pathways. J Neurosci Res 2010; 88(4): 722-34.
  5. Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 2012; 1820(7): 940-8.
  6. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011; 29(4): 341-5.
  7. Xin H, Li Y, Buller B, Katakowski M, Zhang Y, Wang X, et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 2012; 30(7): 1556-64.
  8. Shabbir A, Cox A, Rodriguez-Menocal L, Salgado M, Van Badiavas E. mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem Cells Dev 2015; 24(14): 1635-47.
  9. Yang L, Wu XH, Wang D, Luo CL, Chen LX. Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro. Mol Med Rep 2013; 8(4): 1272-8.
  10. Katerji M, Barada K, Jomaa M, Kobeissy F, Makkawi AK, Abou-Kheir W, et al. Chemosensitivity of U251 cells to the co-treatment of D-penicillamine and copper: Possible implications on Wilson disease patients. Front Mol Neurosci 2017; 10: 10.
  11. Lee M, Liu T, Im W, Kim M. Exosomes from adipose-derived stem cells ameliorate phenotype of Huntington's disease in vitro model. Eur J Neurosci 2016; 44(4): 2114-9.
  12. Waldenstrom A, Genneback N, Hellman U, Ronquist G. Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells. PLoS One 2012; 7(4): e34653.
  13. Lee YS, Jung WY, Heo H, Park MG, Oh SH, Park BG, et al. Exosome-Mediated Ultra-Effective Direct Conversion of Human Fibroblasts into Neural Progenitor-like Cells. ACS Nano 2018; 12(3): 2531-8.
  14. Baranyai T, Herczeg K, Onodi Z, Voszka I, Modos K, Marton N, et al. Isolation of exosomes from blood plasma: qualitative and quantitative comparison of ultracentrifugation and size exclusion chromatography methods. PLoS One 2015; 10(12): e0145686.
  15. Choi EW, Seo MK, Woo EY, Kim SH, Park EJ, Kim S. Exosomes from human adipose-derived stem cells promote proliferation and migration of skin fibroblasts. Exp Dermatol 2018; 27(10): 1170-2.
  16. Hu L, Wang J, Zhou X, Xiong Z, Zhao J, Yu R, et al. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Sci Rep 2016; 6: 32993.
  17. Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A, et al. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J Neurosurg 2015; 122(4): 856-67.
  18. Wang Y, Balaji V, Kaniyappan S, Kruger L, Irsen S, Tepper K, et al. The release and trans-synaptic transmission of Tau via exosomes. Mol Neurodegener 2017; 12(1): 5.
Journal of Isfahan Medical School
Volume 36, Issue 509 - Serial Number 509
November and December 2019
Pages 1578-1583

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History

  • Receive Date: 29 September 2018
  • Revise Date: 02 November 2024
  • Accept Date: 06 April 2022

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