Review: The future of cell therapies and brain repair: Parkinson's disease leads the way

Abstract

During the past 40 years brain tissue grafting techniques have been used both to study fundamental neurobiological questions and to treat neurological diseases. Motor symptoms of Parkinson's disease are largely due to degeneration of midbrain dopamine neurones. Because the nigrostriatal pathology is relatively focused anatomically, Parkinson's disease is considered the ideal candidate for brain repair by neural grafting and dopamine neurone transplantation for it has led the way in the neural transplantation research field. In this mini‐review, we briefly highlight four important areas of development. First, we describe marked functional benefits up to 18 years after transplantation surgery in patients with Parkinson's disease. This is proof‐of‐principle that, using optimal techniques and patient selection, grafted dopamine neurones can work in humans and the duration of the benefit exceeds placebo effects associated with surgery. Second, we describe that eventually protein aggregates containing α‐synuclein, identical to Lewy bodies, develop inside foetal dopamine neurones transplanted to patients with Parkinson's disease. This gives clues about pathogenetic mechanisms operating in Parkinson's disease, and also raises the question whether neural graft function will eventually decline as the result of the disease process. Third, we describe new emerging sources of transplantable dopamine neurones derived from pluripotent stem cells or reprogrammed adult somatic cells. Fourth, we highlight an important European Union‐funded multicentre clinical trial involving transplantation of foetal dopamine neurones in Parkinson's disease. We describe the design of this ongoing trial and how it can impact on the overall future of cell therapy in Parkinson's disease.

Adult Neurogenesis in Neurodegenerative Diseases: Figure 1.

“…Specifically, human pluripotent stem cell -derived neuronal cells might provide a future cellular source for these techniques. Recently, a new trial has been instated that aims at reviving and refining transplantation techniques, funded by the EU as the multicenter project TRANSEURO (Petit et al 2014).…”

Stem Cell Therapy for Brain Tumors

“…With regard to brain repair, unlike ESCs, ASCs offer the potential for transplantation without ethical dilemmas. Neurodegenerative disease may be treated with a variety of ASCs including NSCs, MSCs, HSCs, and stem cells from umbilical cord blood (UCB) [50][51][52][53]. Experimental evidence indicates that the mentioned stem cells can differentiate into neurons and glia [54][55][56].…”

The effect of magnetic nanoparticles on neuronal differentiation of induced pluripotent stem cell-derived neural precursors

“…IPSCs have the potential for studying and treating a wide range of neurological conditions, such as amyotrophic lateral sclerosis, 38 PD, 10 Alzheimer's disease 39 or multiple sclerosis. 40 The promise of stem cell-based therapy for …”

“…8 Human iPSC-derived neural precursors (iPSC-NPs) 9 offer a source for cell transplantation therapy in CNS disorders, while minimizing the risk of tumorigenesis present with pluripotent ESCs and iPSCs. 10,11 For in vivo application and translation into the clinic, alongside standard histological and immunohistochemical methods, there is a need for…”