Title:Early Expression of Neuronal Dopaminergic Markers in a Parkinson’s Disease Model in Rats Implanted with Enteric Stem Cells (ENSCs)
Volume: 19
Issue: 2
Author(s): Carmen Parra-Cid*, Eduardo Orozco-Castillo, Julieta García-López, Elena Contreras-Figueroa, Laura E. Ramos-Languren, Clemente Ibarra, Alfonso Carreón-Rodríguez, Michael Aschner, Mina Königsberg and Abel Santamaría*
Affiliation:
- Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitacion Luis Guillermo Ibarra Ibarra, Mexico City,Mexico
- Laboratorio de Aminoacidos Excitadores, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico City,Mexico
Keywords:
Replacement therapy, stem cells, 6-hydroxydopamine, enteric nervous system, Parkinson’s disease, dopaminergic
markers.
Abstract:
Background: Parkinson’s Disease (PD) is a common neurodegenerative disorder affecting
the dopaminergic (DAergic) system. Replacement therapy is a promising alternative aimed at reconstructing
the cytoarchitecture of affected brain regions in PD. Experimental approaches, such as the
replacement of DAergic neurons with cells obtained from the Enteric Nervous System (ENS) has yet
to be explored.
Objective: To establish and characterize a cell replacement strategy with ENS Cells (ENSCs) in a PD
model in rats.
Methods: Since ENSCs can develop mature DAergic phenotypes, here we cultured undifferentiated
cells from the myenteric plexus of newborn rats, establishing that they exhibit multipotential characteristics.
These cells were characterized and further implanted in the Substantia nigra pars compacta
(SNpc) of adult rats previously lesioned by a retrograde degenerative model produced by intrastriatal
injection of 6-Hydroxydopamine (6-OHDA). DAergic markers were assessed in implants to validate
their viability and possible differentiation once implanted.
Results: Cell cultures were viable, exhibited stem cell features and remained partially undifferentiated
until the time of implant. The retrograde lesion induced by 6-OHDA produced DAergic denervation,
reducing the number of fibers and cells in the SNpc. Implantation of ENSCs in the SNpc of 6-OHDAlesioned
rats was tracked after 5 and 10 days post-implant. During that time, the implant increased selective
neuronal and DAergic markers, Including Microtubule-Associated Protein 2 (MAP-2), Dopamine
Transporter (DAT), and Tyrosine Hydroxylase (TH).
Conclusion: Our novel results suggest that ENSCs possess a differentiating, proliferative and restorative
potential that may offer therapeutic modalities to attenuate neurodegenerative events with the inherent
demise of DAergic neurons.
