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

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.

Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function

“…59 The massive engraftment of TH + cells promoted by NSC treatment with pharmacological concentrations of melatonin would therefore contribute not only to generating neurons in the transplanted tissue, but also to triggering the mechanism which enables NSC-mediated functional recovery. 60 We also show that melatonin-treated NSC transplantation leads to a decrease in Aβ production in transgenic mice and a recovery to the levels observed in control mice. Given these results, it is reasonable to infer that the therapeutic action of engrafted NSCs modifies the deleterious environment which contributes to AD pathology, probably by influencing the affected area through the release of diffusible factors.…”

“…However, the values for dopaminergic neurons recorded after transplantation of NSCs in models of PD, although statistically significant, are frequently very low compared to control groups . The massive engraftment of TH + cells promoted by NSC treatment with pharmacological concentrations of melatonin would therefore contribute not only to generating neurons in the transplanted tissue, but also to triggering the mechanism which enables NSC‐mediated functional recovery …”

Cell replacement therapy is the remedial solution for treating Parkinson’s disease

“…NSCs are capable of self-renewing and generating the nervous system phenotype in embryo and adult, in vivo, they are committed to forming the neural lineage differentiation, oligodendrocytes, and astrocytes (24). Due to the deficiency of NSCs in PD in the affected brain regions shows that NSCs are the appropriate candidate for CRT (24). Hence, by the replacement of NSCs into an impaired brain, either as endogenous NSCs, iNSCs, or stem cell-derived NSCs shows a possible therapeutic mean for PD.…”

“…The establishment of NSCs of multifarious origin, human neural precursor cells would be produced as an immense practical value for both neuroscientists and clinical neural transplantation trials (24). The evaluation of NSCs grafted PD models shows that NSCs combine into the nigrostriatal pathway and restores the projection of substantia nigra to striatum resume DA synthesis and release and relieve PD-like symptoms (25)(26)(27).…”

Mesenchymal stem cells in Parkinson’s disease: Motor and nonmotor symptoms in the early posttransplant period

“…Numerous experimental and clinical studies into PD therapy reference the application of cells of various origins: dopamine-secreting cells, fetal mesencephalon cells, embryonic stem cells, induced pluripotent stem cells, bone marrow stem cells (hematopoietic and mesenchymal cells), stem cells from other sources, and genetically modified cells. [ 28 ] Among them, the use of mesenchymal stem cells (MSCs) is one of the perspective directions of cellular therapy for many neurological disorders for the following reasons: MSCs are easily obtained from various tissues[ 16 ] MSCs are able to independently migrate to the damaged area when introduced into the human body by different routes of administration[ 12 ] MSCs secrete various biological factors necessary for neuroprotection[ 36 ] MSCs can differentiate into neuronal phenotypes under appropriate conditions[ 2 ] Use of MSCs is not accompanied by ethical problems. …”