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Early Expression of Neuronal Dopaminergic Markers in a Parkinson’s Disease Model in Rats Implanted with Enteric Stem Cells (ENSCs)

[ Vol. 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*   Pages 148 - 162 ( 15 )

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.

Keywords:

Replacement therapy, stem cells, 6-hydroxydopamine, enteric nervous system, Parkinson’s disease, dopaminergic markers.

Affiliation:

1 Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, 1 Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, 1 Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, 1 Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Coordinación de Psicología y Neurociencias, División de Estudios Profesionales, Facultad de Psicología, Universidad Nacional Autónoma de México, Mexico City, 1 Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, 5 Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Mexico City, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, Laboratorio de Bioenergética y Envejecimiento Celular, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City



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