Neural stem cells for Parkinson's disease management: Challenges, nanobased support, and prospects

Abstract

Parkinson's disease (PD), characterized by loss of nigrostriatal dopaminergic neurons, is one of the most predominant neurodegenerative diseases affecting the elderly population worldwide. The concept of stem cell therapy in managing neurodegenerative diseases has evolved over the years and has recently rapidly progressed. Neural stem cells (NSCs) have a few key features, including self-renewal, proliferation, and multipotency, which make them a promising agent targeting neurodegeneration. It is generally agreed that challenges for NSC-based therapy are present at every stage of the transplantation process, including preoperative cell preparation and quality control, perioperative procedures, and postoperative graft preservation, adherence, and overall therapy success. In this review, we provided a comprehensive, careful, and critical discussion of experimental and clinical data alongside the pros and cons of NSC-based therapy in PD. Given the state-of-the-art accomplishments of stem cell therapy, gene therapy, and nanotechnology, we shed light on the perspective of complementing the advantages of each process by developing nano-stem cell therapy, which is currently a research hotspot. Although various obstacles and challenges remain, nano-stem cell therapy holds promise to cure PD, however, continuous improvement and development from the stage of laboratory experiments to the clinical application are necessary.

Keywords: Nano-stem cell therapy; Nanomaterials; Neural stem cells; Parkinson’s disease; Synuclein.

Figure 1

Emergence of neural stem cells in the adult brain and alternative sources of neural stem cells. A: The sources of neural stem cells (NSCs) are embryonic stem cells and induced pluripotent stem cells, adult/foetal brain tissue and spinal cord tissue. Also, NSCs can be obtained from somatic cells either by transcription factors and growth factors. The alternative sources of NSCs are foetal and adult nervous systems, umbilical cord blood, bone marrow, peripheral blood, amniotic fluid, Wharton jelly; B: NSCs can have immunomodulatory effects such as cytokine, chemokines, and chemokine receptors secretion and T cell proliferation inhibition. NSCs can have neurotrophic effects such as nerve growth factor, neurotrophin-3, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. NSCs can target secretome and paracrine effects via extracellular vesicles like exosomes. Also, NSCs play a role in neural differentiation; C: NSCs after their transplantation, could migrate, survive, and proliferate in specific brain sites. And NSCs play a role in brain repair mechanisms such as antiapoptotic, anti-inflammatory, and antioxidant. CNS: Central nervous system; BDNF: Brain-derived neurotrophic factor; ESCs: Embryonic stem cells; EVs: Extracellular vesicles; GDNF: Glial cell line-derived neurotrophic factor; iPSCs: Induced pluripotent stem cells; NGF: Nerve growth factor; NT-3: Neurotrophin-3; NSCs: Neural stem cells; TFs: Transcription factors; PD: Parkinson’s disease; TGF: Transforming growth factor. Citation: The parts of the figures were drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/Licenses/by/3.0/).

Figure 2

Application of nanomaterials in stem cell therapy of Parkinson’s disease. Preoperative preparation: Nanomaterials, with their small size, unique physicochemical properties, and capability for surface functionalisation, offer the potential for designed manipulating cell behaviour. A promising strategy is that fabricating the extracellular matrix with biocompatible nanomaterial-based scaffolds with topology simulating the microenvironment. Preoperative phase: nanomaterials capable of suppressing oxidative stress, neuroinflammation, and toxic protein aggregation can act as bioactive nanomedicines addressing the limitations of cell-based therapy for Parkinson’s disease. Moreover, “intelligent” nano-drug delivery systems functionalised by targeting ligands with the controlled release of loaded molecules like growth factor aims to support and expand stem cells for brain repair. At the postoperative stage, nanomaterials, with their unique optical properties, cellular uptake, surface functionalisation, and good biocompatibility, are promising candidates for cell tracking and imaging. MRI: Magnetic resonance imaging. Citation: The parts of the figures were drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/Licenses/by/3.0/).