Induced pluripotent stem cells in Parkinson's disease: scientific and clinical challenges

Abstract

Induced pluripotent stem cells (iPSCs), which greatly circumvent the ethical issue of human embryonic stem cells (ESCs), can be induced to differentiate to dopaminergic (DA) neurons, and hence be used as a human disease model for Parkinson's disease (PD). iPSCs can be also utilised to probe the mechanism, and serve as an ‘in vivo’ platform for drug screening and for cell-replacement therapies. However, any clinical trial approaches should be extensively supported by validated robust biological evidence (based on previous experience with fetal mesencephalic transplantation), in particular, the production and selection of the ‘ideal’ neurons (functional units with no oncological risk), together with the careful screening of appropriate candidates (such as genetic carriers), with inbuilt safeguards (safety studies) in the evaluation and monitoring (functional neuroimaging of both DA and non-DA system) of trial subjects. While iPSCs hold great promise for PD, there are still numerous scientific and clinical challenges that need to be surmounted before any clinical application can be safely introduced.

Resolution of Reprogramming Transition States by Single Cell RNA-Sequencing

“…Reprogramming of somatic cells to a pluripotent state represents a breakthrough for both regenerative medicine and biology (1)(2)(3)(4)(5). For regenerative medicine, reprogramming enables the generation of patient-specific functional cells that can help cure diseases such as Parkinson's disease and spinal cord injury (6)(7)(8)(9)(10)(11). For basic biology, reprogramming has provided valuable insight into how cell fate and cell fate transitions are regulated (12,13).…”

Recent Advances in the Treatment of Cerebellar Disorders

“…For instance, human embryonic stem cells (hESCs) have high proliferative capacity and can grow rapidly to form tumor-like structure of neuroepithelial cells [153]. Although human induced pluripotent (hIPS) stem cells are promising, their use requires Myc and KLf4 reprogramming factors, but these are oncogene factors [154]. Furthermore, the non-self immature cells can elicit autoimmune responses [138].…”

Advances in Stem Cell Research- A Ray of Hope in Better Diagnosis and Prognosis in Neurodegenerative Diseases

“…Mechanistic and pathophysiological studies have given us a deep understanding of the disease. PD is generally associated with a disrupted calcium homeostasis, inflammation, disrupted kinase pathways, generation of reactive oxygen species, and dysfunctional mitochondria (Schapira et al, 2014; Xiao et al, 2016). Animal and cellular models have given us a deep understanding of the disease but data generated is not fully applicable to human subjects due to difference in disease pathogenesis of animals and humans (Devine et al, 2011).…”

“…The successful differentiation of fibroblasts into the DA neurons are reported in literature and has paved way for potential disease modeling (Caiazzo et al, 2011; Kim et al, 2014). The stem cell technology can be used to identify the biochemical markers of the disease and can thus help in the diagnosis of early PD (Xiao et al, 2016). …”