A Comprehensive Analysis of Protocols for Deriving Dopaminergic Neurons from Human Pluripotent Stem Cells

The potential applications of human embryonic and induced pluripotent stem cells has led to immense interest in developing new protocols to differentiate specific cell types or modifying existing protocols. To investigate to what extent and why new protocols for the same cell types are developed and adopted, we systematically evaluated 158 publications (2004‐2017) that differentiated human stem cells into dopaminergic neurons. We categorized each article by degree of novelty and recorded motivations for protocol development. 74 novel or modified protocols were developed. Most (65%) were not used again in subsequent studies. Diverse motivations were recorded and performance of new methods was assessed with substantially different approaches across studies. There was improvement over time in yield of neuron production, but not in yield of dopaminergic neurons or time required for getting neurons. Standardized reporting of performance metrics may help rational choice of the best methods. Stem Cells Translational Medicine 2019;8:366–374

[1]  Gaurav Pandey,et al.  Analysis of Transcriptional Variability in a Large Human iPSC Library Reveals Genetic and Non-genetic Determinants of Heterogeneity. , 2017, Cell stem cell.

[2]  S. Dunnett,et al.  Predictive Markers Guide Differentiation to Improve Graft Outcome in Clinical Translation of hESC-Based Therapy for Parkinson’s Disease , 2017, Cell stem cell.

[3]  Åsa K. Björklund,et al.  Single-Cell Analysis Reveals a Close Relationship between Differentiating Dopamine and Subthalamic Nucleus Neuronal Lineages. , 2017, Cell stem cell.

[4]  John P. A. Ioannidis,et al.  A manifesto for reproducible science , 2017, Nature Human Behaviour.

[5]  H. Schöler,et al.  Molecular Obstacles to Clinical Translation of iPSCs. , 2016, Cell stem cell.

[6]  Timothy Caulfield,et al.  Confronting stem cell hype , 2016, Science.

[7]  Richard T. Lee,et al.  Setting Global Standards for Stem Cell Research and Clinical Translation: The 2016 ISSCR Guidelines , 2016, Stem cell reports.

[8]  Iveta Simera,et al.  A history of the evolution of guidelines for reporting medical research: the long road to the EQUATOR Network , 2016, Journal of the Royal Society of Medicine.

[9]  John P. A. Ioannidis,et al.  How to Make More Published Research True , 2014, PLoS medicine.

[10]  Yi Zhang,et al.  Genetic and epigenetic variations in iPSCs: potential causes and implications for application. , 2013, Cell stem cell.

[11]  D. Moher,et al.  Transparent and accurate reporting increases reliability, utility, and impact of your research: reporting guidelines and the EQUATOR Network , 2010, BMC medicine.

[12]  James A Thomson,et al.  Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency , 2010, Proceedings of the National Academy of Sciences.

[13]  Iveta Simera,et al.  Helping editors, peer reviewers and authors improve the clarity, completeness and transparency of reporting health research , 2008, BMC medicine.

[14]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2007, Cell.

[15]  R. de Kanter,et al.  Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction , 2006, Expert opinion on drug metabolism & toxicology.

[16]  C. Hughes,et al.  Of Mice and Not Men: Differences between Mouse and Human Immunology , 2004, The Journal of Immunology.

[17]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[18]  Per Capita,et al.  About the authors , 1995, Machine Vision and Applications.

[19]  B. Thiers Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2008 .