Journal of Embryo Transfer (한국수정란이식학회지)

The Korean Society of Embryo Transfer (한국수정란이식학회)
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An Increase in Mesenchymal Stem Cells Expressing Nestin in Bone-Marrow-Derived Primary Cells Stimulates Neurogenic Differentiation in Rat

  • Han, Na Rae (Department of Animal Life Science, Kangwon National University) ;
  • Lee, Hyun (Department of Animal Life Science, Kangwon National University) ;
  • Yun, Jung Im (Division of Animal Resource Science, Kangwon National University) ;
  • Kim, Choonghyo (Department of Neurosurgery, Kangwon National University Hospital, School of Medicine, Kangwon National University) ;
  • Hwang, Jae Yeon (Department of Cellular and Molecular Physiology, Yale School of Medicine) ;
  • Park, Kyu Hyun (Department of Animal Life Science, Kangwon National University) ;
  • Lee, Seung Tae (Department of Animal Life Science, Kangwon National University)
  • Received : 2017.02.10
  • Accepted : 2017.04.27
  • Published : 2017.06.30
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Abstract

Mesenchymal stem cells (MSCs) have been considered an alternative source of neuronal lineage cells, which are difficult to isolate from brain and expand in vitro. Previous studies have reported that MSCs expressing Nestin ($Nestin^+$ MSCs), a neuronal stem/progenitor cell marker, exhibit increased transcriptional levels of neural development-related genes, indicating that $Nestin^+$ MSCs may exert potential with neurogenic differentiation. Accordingly, we investigated the effects of the presence of $Nestin^+$ MSCs in bone-marrow-derived primary cells (BMPCs) on enhanced neurogenic differentiation of BMPCs by identifying the presence of $Nestin^+$ MSCs in uncultured and cultured BMPCs. The percentage of $Nestin^+$ MSCs in BMPCs was measured per passage by double staining with Nestin and CD90, an MSC marker. The efficiency of neurogenic differentiation was compared among passages, revealing the highest and lowest yields of $Nestin^+$ MSCs. The presence of $Nestin^+$ MSCs was identified in BMPCs before in vitro culture, and the highest and lowest percentages of $Nestin^+$ MSCs in BMPCs was observed at the third (P3) and fifth passages (P5). Moreover, significantly the higher efficiency of differentiation into neurons, oligodendrocyte precursor cells and astrocytes was detected in BMPCs at P3, compared with P5. In conclusion, these results demonstrate that neurogenic differentiation can be enhanced by increasing the proportion of $Nestin^+$ MSCs in cultured BMPCs.

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References

  1. Armstrong L, Al-Aama J, Stojkovic M, Lako M. 2014. Concise review: the epigenetic contribution to stem cell ageing: can we rejuvenate our older cells? Stem Cells 32:2291-2298. https://doi.org/10.1002/stem.1720
  2. Augello A, De Bari C. 2010. The regulation of differentiation in mesenchymal stem cells. Hum. Gene. Ther. 21:1226-1238. https://doi.org/10.1089/hum.2010.173
  3. Bae KS, Park JB, Kim HS, Kim DS, Park DJ, Kang SJ. 2011. Neuron-like differentiation of bone marrow-derived mesenchymal stem cells. Yonsei Med. J. 52:401-412. https://doi.org/10.3349/ymj.2011.52.3.401
  4. Croft AP, Przyborski SA. 2009. Mesenchymal stem cells expressing neural antigens instruct a neurogenic cell fate on neural stem cells. Exp. Neurol. 216:329-341. https://doi.org/10.1016/j.expneurol.2008.12.010
  5. Eshghi S, Schaffer DV. 2008. Engineering microenvironments to control stem cell fate and function. Stem Book, Harvard Stem Cell Institute, Cambridge, MA.
  6. Farrell MJ, Shin JI, Smith LJ, Mauck RL. 2015. Functional consequences of glucose and oxygen deprivation on engineered mesenchymal stem cell-based cartilage constructs. Osteoarthritis Cartilage 23:134-142. https://doi.org/10.1016/j.joca.2014.09.012
  7. Fu L, Zhu L, Huang Y, Lee TD, Forman SJ, Shih CC. 2008. Derivation of neural stem cells from mesenchymal stem cells: evidence for a bipotential stem cell population. Stem Cells. Dev. 17:1109-1121. https://doi.org/10.1089/scd.2008.0068
  8. Huat TJ, Khan AA, Pati S, Mustafa Z, Abdullah JM, Jaafar H. 2014. IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells. BMC Neurosci. 15:91. https://doi.org/10.1186/1471-2202-15-91
  9. Jakel RJ, Schneider BL, Svendsen CN. 2004. Using human neural stem cells to model neurological disease. Nat. Rev. Genet. 5:136-144. https://doi.org/10.1038/nrg1268
  10. Kim SU, de Vellis J. 2009. Stem cell-based cell therapy in neurological diseases: a review. J. Neurosci. Res. 87:2183-2200. https://doi.org/10.1002/jnr.22054
  11. Lee IS, Jung K, Kim M, Park KI. 2010. Neural stem cells: properties and therapeutic potentials for hypoxic-ischemic brain injury in new born infants. Pediatr. Int. 52:855-865. https://doi.org/10.1111/j.1442-200X.2010.03266.x
  12. Lee ST, Gong SP, Yum KE, Lee EJ, Lee CH, Choi JH, Kim DY, Han H, Kim KS, Hysolli E, Ahn JY, Park IH, Han JY, Jeong JW, Lim JM. 2013. Transformation of somatic cells into stem cell-like cells under a stromal niche. FASEB J. 27:2644-2656. https://doi.org/10.1096/fj.12-223065
  13. Mothe AJ, Zahir T, Santaguida C, Cook D, Tator CH. 2011. Neural stem/progenitor cells from the adult human spinal cord are multipotent and self-renewing and differentiate after transplantation. PLoS One 6:e27079. https://doi.org/10.1371/journal.pone.0027079
  14. Nam H, Lee KH, Nam DH, Joo KM. 2015. Adult human neural stem cell therapeutics: Current developmental status and prospect. World J. Stem Cells 7:126-136. https://doi.org/10.4252/wjsc.v7.i1.126
  15. Ramos-Zuniga R, Gonzalez-Perez O, Macias-Ornelas A, Capilla-Gonzalez V, Quinones-Hinojosa A. 2012. Ethical implications in the use of embryonic and adult neural stem cells. Stem Cells Int. 2012:470949.
  16. Smith R, Bagga V, Fricker-Gates RA. 2003. Embryonic neural progenitor cells: the effects of species, region, and culture conditions on long-term proliferation and neuronal differentiation. J. Hematother. Stem Cell Res. 12:713-725. https://doi.org/10.1089/15258160360732731
  17. Suksuphew S, Noisa P. 2015. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases. World J. Stem Cells 7:502-511. https://doi.org/10.4252/wjsc.v7.i2.502
  18. Wislet-Gendebien S, Hans G, Leprince P, Rigo JM, Moonen G, Rogister B. 2005. Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to exitable neuron-like phenotype. Stem Cells 23:392-402. https://doi.org/10.1634/stemcells.2004-0149
  19. Wislet-Gendebien S, Leprince P, Moonen G, Rogister B. 2003. Regulation of neural markers nestin and GFAP expression by cultivated bone marrow stromal cells. J. Cell Sci. 116:3295-3302. https://doi.org/10.1242/jcs.00639