Optimizing Differentiation Protocols for Producing Dopaminergic Neurons from Human Induced Pluripotent Stem Cells for Tissue Engineering Applications: Supplementary Issue: Stem Cell Biology

Overview

Journal Biomark Insights

Publisher Sage Publications

Date 2023 Mar 6

PMID 36876191

Authors

Meghan Robinson

Suk-Yu Yau

Lin Sun

Nicole Gabers

Emma Bibault

Brian R Christie

Stephanie M Willerth

Affiliations

Soon will be listed here.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that results when the dopaminergic neurons (DNs) present in the substantia nigra necessary for voluntary motor control are depleted, making patients with this disorder ideal candidates for cell replacement therapy. Human induced pluripotent stem cells (hiPSCs), obtained by reprogramming adult cells, possess the properties of pluripotency and immortality while enabling the possibility of patient-specific therapies. An effective cell therapy for PD requires an efficient, defined method of DN generation, as well as protection from the neuroinflammatory environment upon engraftment. Although similar in pluripotency to human embryonic stem cells (hESCs), hiPSCs differentiate less efficiently into neuronal subtypes. Previous work has shown that treatment with guggulsterone can efficiently differentiate hESCs into DNs. Our work shows that guggulsterone is able to derive DNs from hiPSCs with comparable efficiency, and furthermore, this differentiation can be achieved inside three-dimensional fibrin scaffolds that could enhance cell survival upon engraftment.

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References

Okita K, Ichisaka T, Yamanaka S . Generation of germline-competent induced pluripotent stem cells. Nature. 2007; 448(7151):313-7. DOI: 10.1038/nature05934. View

Schulz T, Noggle S, Palmarini G, Weiler D, Lyons I, Pensa K . Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture. Stem Cells. 2004; 22(7):1218-38. DOI: 10.1634/stemcells.2004-0114. View

Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V . Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391):1145-7. DOI: 10.1126/science.282.5391.1145. View

Evans M, Kaufman M . Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981; 292(5819):154-6. DOI: 10.1038/292154a0. View

Soldner F, Laganiere J, Cheng A, Hockemeyer D, Gao Q, Alagappan R . Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell. 2011; 146(2):318-31. PMC: 3155290. DOI: 10.1016/j.cell.2011.06.019. View

Bjorklund L, Isacson O . Regulation of dopamine cell type and transmitter function in fetal and stem cell transplantation for Parkinson's disease. Prog Brain Res. 2002; 138:411-20. DOI: 10.1016/S0079-6123(02)38090-7. View

Swistowski A, Peng J, Liu Q, Mali P, Rao M, Cheng L . Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Stem Cells. 2010; 28(10):1893-904. PMC: 2996088. DOI: 10.1002/stem.499. View

Gonzalez R, Garitaonandia I, Abramihina T, Wambua G, Ostrowska A, Brock M . Deriving dopaminergic neurons for clinical use. A practical approach. Sci Rep. 2013; 3:1463. PMC: 3597995. DOI: 10.1038/srep01463. View

Ko J, Mohtaram N, Ahmed F, Montgomery A, Carlson M, Lee P . Fabrication of poly (ϵ-caprolactone) microfiber scaffolds with varying topography and mechanical properties for stem cell-based tissue engineering applications. J Biomater Sci Polym Ed. 2013; 25(1):1-17. DOI: 10.1080/09205063.2013.830913. View

10.

Wernig M, Zhao J, Pruszak J, Hedlund E, Fu D, Soldner F . Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci U S A. 2008; 105(15):5856-61. PMC: 2311361. DOI: 10.1073/pnas.0801677105. View

11.

Mohtaram N, Montgomery A, Willerth S . Biomaterial-based drug delivery systems for the controlled release of neurotrophic factors. Biomed Mater. 2013; 8(2):022001. DOI: 10.1088/1748-6041/8/2/022001. View

12.

Nutt J . Pharmacokinetics and pharmacodynamics of levodopa. Mov Disord. 2008; 23 Suppl 3:S580-4. DOI: 10.1002/mds.22037. View

13.

Yu J, Vodyanik M, Smuga-Otto K, Antosiewicz-Bourget J, Frane J, Tian S . Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007; 318(5858):1917-20. DOI: 10.1126/science.1151526. View

14.

Ross C, Akimov S . Human-induced pluripotent stem cells: potential for neurodegenerative diseases. Hum Mol Genet. 2014; 23(R1):R17-26. PMC: 4170718. DOI: 10.1093/hmg/ddu204. View

15.

Willerth S, Arendas K, Gottlieb D, Sakiyama-Elbert S . Optimization of fibrin scaffolds for differentiation of murine embryonic stem cells into neural lineage cells. Biomaterials. 2006; 27(36):5990-6003. PMC: 1794024. DOI: 10.1016/j.biomaterials.2006.07.036. View

16.

Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E . Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci U S A. 2010; 107(36):15921-6. PMC: 2936617. DOI: 10.1073/pnas.1010209107. View

17.

Cho M, Hwang D, Kim D . Efficient derivation of functional dopaminergic neurons from human embryonic stem cells on a large scale. Nat Protoc. 2008; 3(12):1888-94. DOI: 10.1038/nprot.2008.188. View

18.

Rhee Y, Ko J, Chang M, Yi S, Kim D, Kim C . Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J Clin Invest. 2011; 121(6):2326-35. PMC: 3104759. DOI: 10.1172/JCI45794. View

19.

Lu P, Graham L, Wang Y, Wu D, Tuszynski M . Promotion of survival and differentiation of neural stem cells with fibrin and growth factor cocktails after severe spinal cord injury. J Vis Exp. 2014; (89):e50641. PMC: 4435462. DOI: 10.3791/50641. View

20.

Montgomery A, Wong A, Gabers N, Willerth S . Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds. Biomater Sci. 2015; 3(2):401-13. DOI: 10.1039/c4bm00299g. View