Remarkable migration propensity of dental pulp stem cells towards neurodegenerative milieu: An in vitro analysis

Senthilkumar S 1 , Venugopal C 1 , Parveen S 1 , K S 1 , Rai KS 2 , Kutty BM 3 Show all authors , Dhanushkodi A 4

Affiliations 

  • 1 Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Bangalore, Karnataka, India
  • 2 Dept. of Physiology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
  • 3 Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
  • 4 Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Bangalore, Karnataka, India. Electronic address: ds.anand@manipal.edu
Neurotoxicology, 2020 12;81:89-100.
PMID: 32905802 DOI: 10.1016/j.neuro.2020.08.006

Abstract

Stem cell therapy provides a ray of hope for treating neurodegenerative diseases (ND). Bone marrow mesenchymal stem cells (BM-MSC) were extensively investigated for their role in neuroregeneration. However, drawbacks like painful bone marrow extraction, less proliferation and poor CNS engraftment following systemic injections of BM-MSC prompt us to search for alternate/appropriate source of MSC for treating ND. In this context, dental pulp stem cells (DPSC) could be an alternative to BM-MSC as it possess both mesenchymal and neural characteristic features due to its origin from ectoderm, ease of isolation, higher proliferation index and better neuroprotection. A study on the migration potential of DPSC compared to BM-MSC in a neurodegenerative condition is warranted. Given the neural crest origin, we hypothesize that DPSC possess better migration towards neurodegenerative milieu as compared to BM-MSC. In this prospect, we investigated the migration potential of DPSC in an in vitro neurodegenerative condition. Towards this, transwell, Matrigel and chorioallantoic membrane (CAM) migration assays were carried-out by seeding hippocampal neurons in the lower chamber and treated with 300 μM kainic acid (KA) for 6 h to induce neurodegeneration. Subsequently, the upper chamber of transwell was loaded with DPSC/BM-MSC and their migration potential was assessed following 24 h of incubation. Our results revealed that the migration potential of DPSC/BM-MSC was comparable in non-degenerative condition. However, following injury the migration potential of DPSC towards the degenerating site was significantly higher as compared to BM-MSC. Furthermore, upon exposure of naïve DPSC/BM-MSCs to culture medium derived from neurodegenerative milieu resulted in significant upregulation of homing factors like SDF-1alpha, CXCR-4, VCAM-1, VLA-4, CD44, MMP-2 suggesting that the superior migration potential of DPSC might be due to prompt expression of homing factors in DPSC compared to BM-MSCs.

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