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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 24, 2017; 7(3): 179-192
Published online Jun 24, 2017. doi: 10.5500/wjt.v7.i3.179
Historical perspective of cell transplantation in Parkinson’s disease
Alejandra Boronat-García, Magdalena Guerra-Crespo, René Drucker-Colín
Alejandra Boronat-García, Magdalena Guerra-Crespo, René Drucker-Colín, Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México 04510, México
Author contributions: Boronat-García A and Guerra-Crespo M contributed equally to this work; Boronat-García A, Guerra-Crespo M and Drucker-Colín R wrote the paper.
Supported by DGAPA-PAPIIT, No. IN207116; and CONACyT, No. 179927.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: René Drucker-Colín, PhD, Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Ciudad de México 04510, México. drucker@unam.mx
Telephone: +52-5-6225732
Received: January 20, 2017
Peer-review started: January 20, 2017
First decision: April 14, 2017
Revised: May 8, 2017
Accepted: May 12, 2017
Article in press: May 15, 2017
Published online: June 24, 2017
Processing time: 153 Days and 22.6 Hours
Abstract

Cell grafting has been considered a therapeutic approach for Parkinson’s disease (PD) since the 1980s. The classical motor symptoms of PD are caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrement in dopamine release in the striatum. Consequently, the therapy of cell-transplantation for PD consists in grafting dopamine-producing cells directly into the brain to reestablish dopamine levels. Different cell sources have been shown to induce functional benefits on both animal models of PD and human patients. However, the observed motor improvements are highly variable between individual subjects, and the sources of this variability are not fully understood. The purpose of this review is to provide a general overview of the pioneering studies done in animal models of PD that established the basis for the first clinical trials in humans, and compare these with the latest findings to identify the most relevant aspects that remain unanswered to date. The main focus of the discussions presented here will be on the mechanisms associated with the survival and functionality of the transplants. These include the role of the dopamine released by the grafts and the capacity of the grafted cells to extend fibers and to integrate into the motor circuit. The complete understanding of these aspects will require extensive research on basic aspects of molecular and cellular physiology, together with neuronal network function, in order to uncover the real potential of cell grafting for treating PD.

Keywords: Parkinson’s disease; Cell replacement; Animal models; Nigrostriatal pathway; Striatum; Dopaminergic loss

Core tip: The first studies on cell transplantation for Parkinson’s disease were published during the early 80s. Since then, it has been shown that different cell types induce functional benefits but with high variability among subjects. Here, we first provide a general overview of the field during its early years. Then, we discuss some factors associated with the functionality of the graft based on the latest findings, and highlight the importance of understanding basic aspects (e.g., factors influencing graft integration) which ultimately could contribute to reducing the variability of the functional outcome-an important requirement for its application in the clinic.