HISTOLOGICAL AND ELECTROPHYSIOLOGICAL CHARACTERIZATION OF NEURAL-PRECONDITIONED HUMAN DENTAL PULP STEM CELLS AFTER THEIR GRAFT INTO C57BL/6J HIPPOCAMPUS

Stem cell grafting into the central nervous system has developed into a major avenue for replacing the neurons damage and lost in neurodegenerative diseases. In this context, human dental pulp stem cells (hDPSCs) constitute a promising alternative due to their unique features including their neural crest origin and their capacity to in vitro differentiate into functional neuron like cells. While transplantation represents a key tool for assessing the in vivo functionality of stem cells, little is known about neural differentiated hDPSCs integration into the host brain circuitry. In this study, we assessed the ability of hDPSC-derived cells to integrate within the mouse hippocampus.
hDPSCs were transduced with lentiviral particles containing a green fluorescent protein (GFP) reporter gene. GFP positive cells were injected into the CA1 hippocampal region of C57BL/6J mice. One month after graft, cells survival and integration into the host tissue were determined by histological and electrophysiological analysis.
After lentiviral transduction in vitro stable populations of GFP⁺-hDPSCs were generated. In non-immunosuppressed C57BL/6J mice, grafted GFP⁺-hDPSCs survived and were detected into the hippocampal region one month after transplantation; furthermore, most of the cells displayed an immature doublecortin (DCX) positive neuroblast-like phenotype with yet immature electrophysiological properties. Similarly to tiny granular cells, grafted hDPSCs could trigger immature single action potentials and showed high input resistances and low capacitance values.
Our study showcases the potential of an easily accessible human stem cell source for nerve tissue engineering and sheds light on hDPSCs in vivo neurodifferentiation and brain grafting potential.