Abstract
Dopaminergic (DA) neurons are involved in many critical functions within the central nervous system (CNS), and dopamine neurotransmission impairment underlies a wide range of disorders from motor control deficiencies, such as Parkinson’s disease (PD), to psychiatric disorders, such as alcoholism, drug addictions, bipolar disorders, schizophrenia and depression. Neural stem cell-based technology has potential to play an important role in developing efficacious biological and small molecule therapeutic products for disorders with dopamine dysregulation. Various methods of differentiating DA neurons from pluripotent stem cells have been reported. In this chapter, we describe a simple technique using dopamine-inducing factors (DIFs) to differentiate neural stem cells (NSCs), isolated from induced pluripotent stem cells (iPSCs) into DA neurons.
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References
Isacson O (2003) The production and use of cells as therapeutic agents in neurodegenerative diseases. Lancet Neurol 2(7):417–424
Brazel CY, Rao MS (2004) Aging and neuronal replacement. Ageing Res Rev 3(4):465–483
Björklund A et al (1987) Mechanisms of action of intracerebral neural implants: studies on nigral and striatal grafts to the lesioned striatum. TINS 10(12):509–516
Jonsson ME et al (2009) Identification of transplantable dopamine neuron precursors at different stages of midbrain neurogenesis. Exp Neurol 219(1):341–354
Carvey PM et al (2001) A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: a source of cells for transplantation in Parkinson’s disease. Exp Neurol 171(1):98–108
Zeng X et al (2004) Dopaminergic differentiation of human embryonic stem cells. Stem Cells 22(6):925–940
Chiba S et al (2008) Noggin enhances dopamine neuron production from human embryonic stem cells and improves behavioral outcome after transplantation into Parkinsonian rats. Stem Cells 26(11):2810–2820
Hedlund E et al (2008) Embryonic stem cell-derived Pitx3-enhanced green fluorescent protein midbrain dopamine neurons survive enrichment by fluorescence-activated cell sorting and function in an animal model of Parkinson’s disease. Stem Cells 26(6):1526–1536
Kriks S et al (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480(7378):547–551
Arenas E (2010) Towards stem cell replacement therapies for Parkinson’s disease. Biochem Biophys Res Commun 396(1):152–156
O'Keeffe FE et al (2008) Induction of A9 dopaminergic neurons from neural stem cells improves motor function in an animal model of Parkinson’s disease. Brain 131(Pt 3):630–641
Mendez I et al (2008) Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years. Nat Med 14(5):507–509
Deierborg T et al (2008) Emerging restorative treatments for Parkinson's disease. Prog Neurobiol 85(4):407–432
Redmond DE Jr et al (2007) Behavioral improvement in a primate Parkinson’s model is associated with multiple homeostatic effects of human neural stem cells. Proc Natl Acad Sci U S A 104(29):12175–12180
Sonntag KC et al (2007) Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin. Stem Cells 25(2):411–418
Ko JY et al (2007) Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons. J Neurochem 103(4):1417–1429
Yasuhara T et al (2006) Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson’s disease. J Neurosci 26(48):12497–12511
Lindvall O, Kokaia Z (2006) Stem cells for the treatment of neurological disorders. Nature 441(7097):1094–1096
Mendez I et al (2005) Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease. Brain 128(Pt 7):1498–1510
Correia AS et al (2005) Stem cell-based therapy for Parkinson’s disease. Ann Med 37(7):487–498
Bjorklund A (2005) Cell therapy for Parkinson’s disease: problems and prospects. Novartis Found Symp 265:174–186 Discussion 187, 204–211
Roy NS et al (2006) Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat Med 12(11):1259–1268
Armstrong RJ et al (2003) Transplantation of expanded neural precursor cells from the developing pig ventral mesencephalon in a rat model of Parkinson’s disease. Exp Brain Res 151(2):204–217
Ben-Hur T et al (2004) Transplantation of human embryonic stem cell-derived neural progenitors improves behavioral deficit in Parkinsonian rats. Stem Cells 22(7):1246–1255
Borlongan CV, Sanberg PR (2002) Neural transplantation for treatment of Parkinson’s disease. Drug Discov Today 7(12):674–682
Daadi MM et al (2012) Dopaminergic neurons from midbrain-specified human embryonic stem cell-derived neural stem cells engrafted in a monkey model of Parkinson’s disease. PLoS One 7(7):e41120
Grealish S et al (2010) The A9 dopamine neuron component in grafts of ventral mesencephalon is an important determinant for recovery of motor function in a rat model of Parkinson’s disease. Brain 133(Pt 2):482–495
Kim JH et al (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418(6893):50–56
Lee SH et al (2000) Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 18(6):675–679
Kawasaki H et al (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28(1):31–40
Perrier AL et al (2004) Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci U S A 101(34):12543–12548
Hong S et al (2008) Neural precursors derived from human embryonic stem cells maintain long-term proliferation without losing the potential to differentiate into all three neural lineages, including dopaminergic neurons. J Neurochem 104(2):316–324
Yan Y et al (2005) Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23(6):781–790
Schulz TC et al (2004) Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture. Stem Cells 22(7):1218–1238
Vazin T et al (2009) A novel combination of factors, termed SPIE, which promotes dopaminergic neuron differentiation from human embryonic stem cells. PLoS One 4(8):e6606
Hayashi H et al (2008) Meningeal cells induce dopaminergic neurons from embryonic stem cells. Eur J Neurosci 27(2):261–268
Cho MS et al (2008) Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci U S A 105(9):3392–3397
Ko JY et al (2009) Conditions for tumor-free and dopamine neuron-enriched grafts after transplanting human ES cell-derived neural precursor cells. Mol Ther 17(10):1761–1770
Ueno M et al (2006) Neural conversion of ES cells by an inductive activity on human amniotic membrane matrix. Proc Natl Acad Sci U S A 103(25):9554–9559
Kim DW et al (2006) Stromal cell-derived inducing activity, Nurr1, and signaling molecules synergistically induce dopaminergic neurons from mouse embryonic stem cells. Stem Cells 24(3):557–567
Cai J et al (2009) The role of Lmx1a in the differentiation of human embryonic stem cells into midbrain dopamine neurons in culture and after transplantation into a Parkinson’s disease model. Stem Cells 27(1):220–229
Acknowledgment
This work was supported by NeoNeuron LLC.
Disclosures: Dr. Marcel M. Daadi is founder of the biotech company NeoNeuron.
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Daadi, M.M. (2019). Differentiation of Neural Stem Cells Derived from Induced Pluripotent Stem Cells into Dopaminergic Neurons. In: Daadi, M. (eds) Neural Stem Cells. Methods in Molecular Biology, vol 1919. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9007-8_7
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DOI: https://doi.org/10.1007/978-1-4939-9007-8_7
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