A Compendium of Preparation and Application of Stem Cells in Parkinson's Disease: Current Status and Future Prospects.

Yan Shen,Tao Wang,Ling Liu,Guoxin Zhang,Xiaoyun Xu,Nian Xiong,Haiyang Jiang,Zhicheng Lin,Jinsha Huang,Chao Han,Jie Li

doi:10.3389/fnagi.2016.00117

Abstract

Parkinson's Disease (PD) is a progressively neurodegenerative disorder, implicitly characterized by a stepwise loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and explicitly marked by bradykinesia, rigidity, resting tremor and postural instability. Currently, therapeutic approaches available are mainly palliative strategies, including L-3,4-dihydroxy-phenylalanine (L-DOPA) replacement therapy, DA receptor agonist and deep brain stimulation (DBS) procedures. As the disease proceeds, however, the pharmacotherapeutic efficacy is inevitably worn off, worse still, implicated by side effects of motor response oscillations as well as L-DOPA induced dyskinesia (LID). Therefore, the frustrating status above has propeled the shift to cell replacement therapy (CRT), a promising restorative therapy intending to secure a long-lasting relief of patients' symptoms. By far, stem cell lines of multifarious origins have been established, which can be further categorized into embryonic stem cells (ESCs), neural stem cells (NSCs), induced neural stem cells (iNSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). In this review, we intend to present a compendium of preparation and application of multifarious stem cells, especially in relation to PD research and therapy. In addition, the current status, potential challenges and future prospects for practical CRT in PD patients will be elaborated as well.

Highlights

Parkinson’s Disease (PD) is one of the most prevalent neurodegenerative disorders, second only to Alzheimer’s Disease, affecting approximately 1% of the population over the age of 60 and 4% over 80 (de Lau and Breteler, 2006)
Subordinate to Good Manufacturing Practice (GMP) standards; Here in this review, we propose to present an elaborate compendium of the preparation and application of stem cell lines, especially embryonic stem cells (ESCs), neural stem cells (NSCs)/neural progenitor cells (NPCs), induced neural stem cells (iNSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) for research and therapy of PD
Stem cell based cell replacement therapy (CRT) has emerged as a restorative therapy for PD

Summary

INTRODUCTION

Parkinson’s Disease (PD) is one of the most prevalent neurodegenerative disorders, second only to Alzheimer’s Disease, affecting approximately 1% of the population over the age of 60 and 4% over 80 (de Lau and Breteler, 2006). Apart from morphogens above, there exist several tissue culture protocols available to induce production of A9 DA neurons from hESCs, including co-culturing feeder cells (Kawasaki et al, 2000; Perrier et al, 2004; Zeng et al, 2004; Park et al, 2005; Brederlau et al, 2006), soluble growth factors (Lee et al, 2000; Schulz et al, 2004; Takagi et al, 2005; Yan et al, 2005; Yang et al, 2008), genetic manipulation (Kim et al, 2002; Chung et al, 2005; Andersson et al, 2006) and specific combination of FIGURE 2 | Flow chart of the isolation, induced differentiation, and application as a renewable replacement cell source in PD treatment. Several morphogens (such as all-trans RA, SHH, FGF, EGF, BMPs, GDNF) facilitate neural lineage induction (Fraichard et al, 1995; Ciccolini and Svendsen, 1998; Guan et al, 2001; Buytaert-Hoefen et al, 2004; Perrier et al, 2004; Li et al, 2005)

DA phenotype

Expression of TH

Delivery methods

Easily accessible source tissue

Findings

CONCLUSIONS