Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications

Abstract

Many central nervous system (CNS) diseases including stroke, spinal cord injury (SCI), and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting.

Optimizing Stem Cell Therapy after Ischemic Brain Injury

“…NSC, neural stem cell; UC-MSC, umbilical cord-derived mesenchymal stem cell; BMSC, bone marrow stem cell; UC-BSC, umbilical cord blood stem cell; AD-MSC, adipose-derived mesenchymal stem cell; HSC, hematopoietic stem cell; 3D, three-dimensional; VEGF, vascular endothelial growth factor; BDNF, brain derived neurotrophic factor; FGF1, fibroblast growth factor type 1. manipulated to differentiate into phenotypes from all three embryonic layers. 34 Human iPSCs (hiPSCs) have been used for therapeutic solutions regarding central nervous system (CNS) disorders, 35 although their use for ischemic brain injury has remained limited. This cell type has been limited in translational use due to a potential risk for insertional mutagenesis or oncogenesis, production of immune-tolerable cells, and a poor integration into host circuits.…”

“…ESCs and iPSCs have a powerful renewal potential and can be manipulated to differentiate into phenotypes from all three embryonic layers [ 34 ]. Human iPSCs (hiPSCs) have been used for therapeutic solutions regarding central nervous system (CNS) disorders [ 35 ], although their use for ischemic brain injury has remained limited. This cell type has been limited in translational use due to a potential risk for insertional mutagenesis or oncogenesis, production of immune-tolerable cells, and a poor integration into host circuits [ 34 , 36 ].…”

Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

“…iPSCs provide great opportunities for regenerative medicine, disease modeling, and drug discovery [ 55 ]. However, several major disadvantages obstruct the application, namely, genomic modification, teratogenicity, transmission of nonhuman pathogens to humans, and cost and labor of reprogramming process [ 56 ]. Although recent advances in reprogramming footprint-free and xeno-free iPSCs made iPSCs become the most appealing but it is necessary to significantly improve reprogramming technology to overcome the limitations.…”

The Vegetative State and Stem Cells: Therapeutic Considerations

“…Such properties of these reprogramed cells help provide considerable hope that VS and other disease states in which neurodegeneration is a feature might be successfully treated in the future. Indeed, in the 10 years since the seminal work of Takahashi and Yamanaka ( 62 ), significant progress has already occurred in deriving iPSCs suitable for clinical use ( 64 ).…”