Human autologous iPSC–derived dopaminergic progenitors restore motor function in Parkinson’s disease models

Pluripotent Stem Cell Therapies for Parkinson Disease: Present Challenges and Future Opportunities

“…Other subtype selective markers of interest include ALDH1A1, which has been defined as an A9 type marker (Chung et al, 2011;Xi et al, 2012;Song et al, 2020). Both ALDH1A1 and the transcription factor SOX6 have been reported as specific molecular determinants expressed at the mDA neuron progenitor stage, marking precursors that later develop into ventro-lateral A9-type SN neurons (Panman et al, 2014;Blaess and Ang, 2015).…”

“…Without understanding the potential risks and side-effects that could come from "off-target" neuronal or non-neuronal populations, most groups strive to produce highly enriched and defined mDA neuron populations and to eliminate any contaminating cells to assure safety for clinical translation. Several strategies have been proposed to avoid unwanted cells either via enriching floor-plate or later stage mDA precursors using a surface marker (Doi et al, 2014;Samata et al, 2016;Lehnen et al, 2017) or via eliminating remaining undifferentiated hPSCs by exposing cultures during mDA neuron differentiation with natural compound, quercetin (Song et al, 2020). Those studies reported that purified mDA progenitors resulted in more homogenous graft size and mDA neuron density as well as in improved recovering motor dysfunctions in PD animal models than non-sorted cells without evidence of any tumor formation (Doi et al, 2014;Samata et al, 2016;Lehnen et al, 2017).…”

“…The resulting floor-plate derived mDA cells showed the biochemical and electrophysiological properties of mDA neurons in vitro and resulted in more robust survival and function in vivo while reducing the risk of neural overgrowth or teratoma formation ( Kriks et al, 2011 ; Table 1 ). Since those initial studies, several groups have developed independent mDA neuron differentiation paradigms ( Kirkeby et al, 2012 , 2017 ; Sundberg et al, 2013 ; Doi et al, 2014 ; Hallett et al, 2014 ; Steinbeck et al, 2015 ; Chen et al, 2016 ; Niclis et al, 2017 ; Gantner et al, 2020 ; Song et al, 2020 ) but all of those are based on the specification of mDA neurons via a floor-plate intermediate ( Figure 1 ).…”

Tumorigenic and Immunogenic Properties of Induced Pluripotent Stem Cells: a Promising Cancer Vaccine

“…Scientists developed integration-free methods such as adenoviral vectors, Sendai viruses, plasmid vectors, and small-molecule compounds to make reprogramming process safer and more efficient [27][28][29][30][31][32][33][34]. Elimination of residual undifferentiated stem cells was also found to be vital for achieving tumor-free transplantation [35,36]. Researchers created an in vitro selective system to ablate immature proliferating cells by introducing suicide genes into the cells [37].…”

Modeling Parkinson’s Disease Using Induced Pluripotent Stem Cells

“…These cell-sorting technologies maintain the quality of transplanted cells and improve the safety and effectiveness of cell replacement therapy. Multiple animal trials have shown that iPSC transplantation is successful and safe in treating neurological diseases [146][147][148], and human clinical trials of Parkinson's disease using iPSCs are ongoing and observed [149][150][151]. Therefore, the iPSC treatment is expected to become a promising method for PD patients.…”