Acta Scientific Neurology (ASNE) (ISSN: 2582-1121)

Research Article Volume 4 Issue 5

Coculturing NSCs with Melanocyte Increased its Dopamine and Neural Factor Secretion

Ashok Chakraborty1* and Anil Diwan2

1Chief Scientist, Allexcel, Inc., USA 2Chief Executive Officer, Allexcel, Inc., USA

*Corresponding Author: Ashok Chakraborty, Chief Scientist, Allexcel, Inc., USA.

Received: December 11, 2020; Published: April 30, 2021

×

Abstract

Background: Neural stem cells (NSCs) since being a multi-potent neural crest originated cells, are able for self-replication, and differentiation to astrocytes, oligodendrocytes, or neurons. Therefore, it is expected that autologous transplantation of hNSCs to CNS, can be considered as a therapeutic approach for Parkinson's disease (PD). However, growth of human neural stem cells (hNSCs) is very slow, and they senesce after few passages, therefore enough amount of neural cells is very difficult to obtain to treat a number of patients.

Aim: The growth potential and survival length of the neural stem cells have to improved to make it practically feasible to use as a cell therapeutic regiment for PD. At the present time, cell co-cultures have been extensively used in cell functional research. We will study here whether co-culturing NSCs with another neural crest originated cells, Melanocytes (MCs), can increase the proliferation rate and Dopamine synthesis capacity of NSCs.

Methods: We compared the growth potential, synthesis of DOPAmine (DA), Brain-Derived Neurotropic Factor (BDNF) and Glial cell-Derived Neurotropic Factors (GDNF) by NSCs cultured alone and in co-culture system with MCs.

Results: hNSC’s doubling time increases by 2-3 times in co-culture condition. Survival length of hNSCs in co-culture system is beyond 25 passages, whereas senescence occurred after only 5-6 passages when cultured alone. DA production as well as BDNF and GDNF production by hNSCs is much more in co-culture system compared to hNSCs by itself, only.

Conclusion: A possible modification of hNSCs is possible by close association with melanocytes. A further study is required how these changes can be made beyond transient and subtle type.

Keywords: Human Neural Stem Cells (hNSCs); DOPAmine; Dopaminergic Neurons; BDNF; GDNF; Parkinson’s Disease; Melanocytes; Co-Culture System

×

References

  1. Alexander GE. “Biology of Parkinson’s Disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder”. Dialogues in Clinical Neuroscience 3 (2004): 259-280.
  2. Zeng X-S., et al. “Cellular and Molecular Basis of Neurodegeneration in Parkinson Disease”. Frontiers in Aging Neuroscience 10 (2018): 109.
  3. Rodriguez AM., et al. “Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse”. Journal of Experimental Medicine 201 (2005): 1397-1405.
  4. Mosahebi A., et al. “Retroviral labeling of Schwann cells: In vitro characterization and in vivo transplantation to improve peripheral nerve regeneration”. Glia 34 (2001): 8-17.
  5. Shen Q., et al. “Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells”. Science 5675 (2004): 1338-1340.
  6. Sun J., et al. “Endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF activated Notch and Pten signaling”. Developmental Dynamics 9 (2010): 2345-2353.
  7. Du YB., et al. “Wnt3a is critical for endothelial progenitor cell-mediated neural stem cell proliferation and differentiation”. Molecular Medicine Reports 14 (2016): 2473-2482.
  8. Wang G., et al. “Synergistic effect of neural stem cells and olfactory ensheathing cells on repair of adult rat spinal cord injury”. Cell Transplantation10 (2010): 1325-1337.
  9. Luo L., et al. “Niche astrocytes promote the survival, proliferation and neuronal differentiation of co-transplanted neural stem cells following ischemic stroke in rats”. Experimental and Therapeutic Medicine2 (2017): 645-650.
  10. Shi B., et al. “The enhancement of neural stem cell survival and growth by co-culturing with expanded Sertoli cells in vitro”. Biotechnology Progress1 (2012): 196-205.
  11. Lin LF., et al. “GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons”. Science 1260 (1993): 1130-1132.
  12. Hyman C., et al. “BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra”. Nature 6315 (1991): 230-232.
  13. Klein RL., et al. “Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer”. Brain Research 847 (1999): 314-320.
  14. Bespalov MM and Saarma M. “GDNF family receptor complexes are emerging drug targets”. Trends in Pharmacological Sciences 28 (2007): 68-74.
  15. Chao MV. “Neurotrophins and their receptors: a convergence point for many signaling pathways”. Nature Reviews Neuroscience 4 (2003): 299-309.
  16. Chao MV., et al. “Neurotrophin signalling in health and disease”. Clinical Science (Lond) 110 (2006): 167-173.
  17. Akerud P., et al. “Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson's disease”. Journal of Neuroscience 21 (2001): 8108-8118.
  18. Crouch SP., et al. “The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity”. Journal of Immunological Methods 160 (1993): 81-88.
  19. Chakraborty A and Diwan A. “Selection of Cells for Parkinson’s Disease Cell-Therapy”. International Journal of Stem cell Research and Therapy 6 (2019): 063.
  20. Erickson JT., et al. “Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor Are Required Simultaneously for Survival of Dopaminergic Primary Sensory Neurons In Vivo”. The Journal of Neuroscience 2 (2001): 581-589.
  21. Chakraborty A and Diwan A. “Autocrine and paracrine stimulation of dopamine secretion by human neural stem cells: Role BDNF and GDNF”. Neurology and Neuroscience Reports 3 (2020): 1-6.
  22. Deierborg T., et al. “Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes”. Neuroscience 4 (2010): 1386-1396.
  23. Habisch HJ., et al. “Neuroectodermally converted human mesenchymal stromal cells provide cytoprotective effects on neural stem cells and inhibit their glial differentiation”. Cytotherapy 12 (2010): 491-504.
  24. Lee H., et al. “Bone-marrow-derived mesenchymal stem cells promote proliferation and neuronal differentiation of Niemann-Pick type C mouse neural stem cells by upregulation and secretion of CCL2”. Human Gene Therapy7 (2013): 655-669.
  25. Wang G., et al. “Synergistic effect of neural stem cells and olfactory en-sheathing cells on repair of adult rat spinal cord injury”. Cell Transplantation10 (2010): 1325-1337.
  26. Ramon-Cueto A and Valverde F. “Olfactory bulb ensheathing glia: a unique cell type with axonal growth-promoting properties”. Glia3 (1995): 163-173.
  27. Leibrock J., et al. “Molecular cloning and expression of brain-derived neurotrophic factor”. Nature 341 (1989): 149-152.
  28. Squinto SP., et al. “trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor”. Cell 65 (1991): 885-893.
  29. An YH., et al. “Effect of rat Schwann cell secretion on proliferation and differentiation of human neural stem cells”. Biomedical and Environmental Sciences 16 (2003): 90-94.
  30. Krieglstein K., et al. “Glial cell line-derived neurotrophic factor requires transforming growth factor-beta for exerting its full neurotrophic potential on peripheral and CNS neurons”. Journal of Neuroscience23 (1998): 9822-9834.
  31. Airaksinen M and Saarma M. “The GDNF family: Signalling, biological functions and therapeutic value”. Nature Reviews Neuroscience 3 (2002): 383-394.
  32. Saarma M. “GDNF - a stranger in the TGF-beta superfamily?” European Journal of Biochemistry 24 (2000): 6968-6971.
  33. Lei Z., et al. “Signaling of glial cell line-derived neurotrophic factor and its receptor GFRα1 induce Nurr1 and Pitx3 to promote survival of grafted midbrain-derived neural stem cells in a rat model of Parkinson disease”. Journal of Neuropathology and Experimental Neurology70 (2011): 736-747.
  34. Roussa E and Krieglstein K. “Induction and specification of midbrain dopaminergic cells: focus on SHH, FGF8 and TGF-beta”. Cell Tissue Research1 (2004): 23-33.
  35. Peng C., et al. “Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons”. Journal of Neuroscience 31 (2011): 12802-12815.
  36. Zhu SY., et al. “Identification of a Vav2-dependent mechanism for GDNF/Ret control of mesolimbic DAT trafficking”. Nature Neuroscience 18 (2015): 1084-1093.
  37. Consales C., et al. “GDNF signaling in embryonic midbrain neurons in vitro”. Brain Research 1159 (2007): 28-39.
  38. Christophersen NS., et al. “Midbrain expression of Delta-like 1 homologue is regulated by GDNF and is associated with dopaminergic differentiation”. Experimental Neurology 204 (2007): 791-801.
  39. Feng L., et al. “Differential effects of GDNF and BDNF on cultured ventral mesencephalic neurons”. Molecular Brain Research 66 (1999): 62-70.
  40. Pothos EN., et al. “Presynaptic recording of quanta from midbrain dopamine neurons and modulation of the quantal size”. Journal of Neuroscience 18 (1998): 4106-4118.
  41. Richardson RM., et al. “Interventional MRI-guided putaminal delivery of AAV2-GDNF for a planned clinical trial in Parkinson’s disease”. Molecular Therapy 19 (2011): 1048-1057.
  42. Thomsen GM., et al. “The past, present and future of stem cell clinical trials for ALS”. Experimental Neurology 262 (2014): 127-137.
  43. Rolan PE., et al. “First-in-human, double-blind, placebo-controlled, randomized, dose-escalation study of BG00010, a glial cell line-derived neurotrophic factor family member, in subjects with unilateral sciatica”. PLoS One 10 (2015): e0125034.
×

Citation

Citation: Ashok Chakraborty and Anil Diwan. “Coculturing NSCs with Melanocyte Increased it’s Dopamine and Neural Factor Secretion". Acta Scientific Neurology 4.2 (2021): 70-78.




Metrics

Acceptance rate32%
Acceptance to publication20-30 days
Impact Factor0.844

Indexed In




News and Events


  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is August 20, 2021.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of “Best Article of the Issue”.
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.
  • Contact US