Induced Pluripotent Stem Cell Technology and Direct Conversion: New Possibilities to Study and Treat Parkinson's Disease

Overview

Journal Stem Cell Rev Rep

Publisher Springer

Specialty Cell Biology

Date 2012 Apr 25

PMID 22529017

Citations 7

Authors

Reinhard Roessler

Erik Boddeke

Sjef Copray

Affiliations

Soon will be listed here.

Abstract

Recent developments in in vitro disease modeling and regenerative medicine have placed induced pluripotent stem cells (iPSCs) in the center of attention as a unique source to study Parkinson's disease. After only 5 years of intensive research, human iPSCs can be generated without viral integration and under xeno-free conditions. This, combined with increasingly sophisticated methods to differentiate iPSCs into functional dopaminergic (DA) neurons, led us to recapitulate the most important findings concerning the use of iPSC technology as a prospective tool to treat symptoms of Parkinson's disease as well as to obtain insight in disease related cell pathogenesis. Moreover, we touch upon some of the latest discoveries in which patient-derived autologous DA neurons come into even more direct reach thanks to a method that allows transdifferentiation of fibroblasts into DA neurons.

Citing Articles

Selective vulnerability in neurodegenerative diseases.

Fu H, Hardy J, E Duff K Nat Neurosci. 2018; 21(10):1350-1358.

PMID: 30250262 PMC: 6360529. DOI: 10.1038/s41593-018-0221-2.

The essentiality of non-coding RNAs in cell reprogramming.

Luginbuhl J, Sivaraman D, Shin J Noncoding RNA Res. 2018; 2(1):74-82.

PMID: 30159423 PMC: 6096403. DOI: 10.1016/j.ncrna.2017.04.002.

Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

Dennie D, Louboutin J, Strayer D World J Stem Cells. 2016; 8(4):136-57.

PMID: 27114746 PMC: 4835673. DOI: 10.4252/wjsc.v8.i4.136.

Generation of pluripotent stem cells without the use of genetic material.

Higuchi A, Ling Q, Suresh Kumar S, Munusamy M, Alarfaj A, Chang Y Lab Invest. 2014; 95(1):26-42.

PMID: 25365202 DOI: 10.1038/labinvest.2014.132.

Mash1 efficiently reprograms rat astrocytes into neurons.

Ding D, Xu L, Xu H, Li X, Liang Q, Zhao Y Neural Regen Res. 2014; 9(1):25-32.

PMID: 25206740 PMC: 4146312. DOI: 10.4103/1673-5374.125326.

References

Chambers S, Fasano C, Papapetrou E, Tomishima M, Sadelain M, Studer L . Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009; 27(3):275-80. PMC: 2756723. DOI: 10.1038/nbt.1529. View

Kim J, Su S, Wang H, Cheng A, Cassady J, Lodato M . Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell. 2011; 9(5):413-9. PMC: 3210333. DOI: 10.1016/j.stem.2011.09.011. View

Ohi Y, Qin H, Hong C, Blouin L, Polo J, Guo T . Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol. 2011; 13(5):541-9. PMC: 3987913. DOI: 10.1038/ncb2239. View

Karumbayaram S, Novitch B, Patterson M, Umbach J, Richter L, Lindgren A . Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells. 2009; 27(4):806-11. PMC: 2895909. DOI: 10.1002/stem.31. View

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

Roybon L, Hjalt T, Christophersen N, Li J, Brundin P . Effects on differentiation of embryonic ventral midbrain progenitors by Lmx1a, Msx1, Ngn2, and Pitx3. J Neurosci. 2008; 28(14):3644-56. PMC: 6671084. DOI: 10.1523/JNEUROSCI.0311-08.2008. View

Kang L, Wang J, Zhang Y, Kou Z, Gao S . iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell. 2009; 5(2):135-8. DOI: 10.1016/j.stem.2009.07.001. View

Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K . Induced pluripotent stem cells generated without viral integration. Science. 2008; 322(5903):945-9. PMC: 3987909. DOI: 10.1126/science.1162494. View

Nirenberg M, Vaughan R, Uhl G, Kuhar M, Pickel V . The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons. J Neurosci. 1996; 16(2):436-47. PMC: 6578661. View

10.

Zhao X, Li W, Lv Z, Liu L, Tong M, Hai T . iPS cells produce viable mice through tetraploid complementation. Nature. 2009; 461(7260):86-90. DOI: 10.1038/nature08267. View

11.

Park I, Zhao R, West J, Yabuuchi A, Huo H, Ince T . Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2007; 451(7175):141-6. DOI: 10.1038/nature06534. View

12.

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

13.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

14.

Andersson E, Tryggvason U, Deng Q, Friling S, Alekseenko Z, Robert B . Identification of intrinsic determinants of midbrain dopamine neurons. Cell. 2006; 124(2):393-405. DOI: 10.1016/j.cell.2005.10.037. View

15.

Miura K, Okada Y, Aoi T, Okada A, Takahashi K, Okita K . Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol. 2009; 27(8):743-5. DOI: 10.1038/nbt.1554. View

16.

Nunes I, Tovmasian L, Silva R, Burke R, Goff S . Pitx3 is required for development of substantia nigra dopaminergic neurons. Proc Natl Acad Sci U S A. 2003; 100(7):4245-50. PMC: 153078. DOI: 10.1073/pnas.0230529100. View

17.

Meissner A, Wernig M, Jaenisch R . Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol. 2007; 25(10):1177-81. DOI: 10.1038/nbt1335. View

18.

Hanna J, Wernig M, Markoulaki S, Sun C, Meissner A, Cassady J . Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. 2007; 318(5858):1920-3. DOI: 10.1126/science.1152092. View

19.

Nguyen H, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P . LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell. 2011; 8(3):267-80. PMC: 3578553. DOI: 10.1016/j.stem.2011.01.013. View

20.

Nishino K, Toyoda M, Yamazaki-Inoue M, Fukawatase Y, Chikazawa E, Sakaguchi H . DNA methylation dynamics in human induced pluripotent stem cells over time. PLoS Genet. 2011; 7(5):e1002085. PMC: 3102737. DOI: 10.1371/journal.pgen.1002085. View