Top

Published in:

10-11-2023 | Parkinson's Disease | Review Article

Progress in direct reprogramming of dopaminergic cell replacement therapy

Authors: Yuan Yuan Zheng, Hui Xu, Yue Si Wang

Published in: Neurological Sciences | Issue 3/2024

Abstract

Parkinson’s disease (PD) is a gradual neurodegenerative disease. While drug therapy and surgical treatments have been the primary means of addressing PD, they do not offer a cure, and the risks associated with surgical treatment are high. Recent advances in cell reprogramming have given rise to new prospects for the treatment of Parkinson’s disease (PD), with induced pluripotent stem cells (iPSCs), induced dopamine neurons (iDNs), and induced neural stem cells (iNSCs) being created. These cells can potentially be used in the treatment of Parkinson’s disease. On the other hand, this article emphasizes the limits of iPSCs and iNSCs in the context of Parkinson’s disease treatment, as well as approaches for direct reprogramming of somatic cells into iDNs. The paper will examine the benefits and drawbacks of directly converting somatic cells into iDNs.

Surmeier DJ (2018) Determinants of dopaminergic neuron loss in Parkinson’s disease. FEBS J 285(19):3657–3668PubMedPubMedCentralCrossRef

Aquino CC, Fox SH (2015) Clinical spectrum of levodopa-induced complications. Mov Disord 30(1):80–89PubMedCrossRef

Antonini A, Moro E, Godeiro C, Reichmann H (2018) Medical and surgical management of advanced Parkinson’s disease. Mov Disord 33(6):900–908PubMedCrossRef

Han F, Liu Y, Huang J, Zhang X, Wei C (2021) Current approaches and molecular mechanisms for directly reprogramming fibroblasts into neurons and dopamine neurons. Front Aging Neurosci 13:738529PubMedPubMedCentralCrossRef

Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676PubMedCrossRef

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872PubMedCrossRef

Han F, Baremberg D, Gao J, Duan J, Lu X, Zhang N, Chen Q (2015) Development of stem cell-based therapy for Parkinson’s disease. Transl Neurodegener 4:16PubMedPubMedCentralCrossRef

Yamanaka S (2020) Pluripotent stem cell-based cell therapy-promise and challenges. Cell stem cell 27(4):523–531PubMedCrossRef

Hou S, Lu P (2016) Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders. Neural Re-gen Res 11(1):28–31CrossRef

10.

Ford E, Pearlman J, Ruan T, Manion J, Waller M, Neely GG, Caron L (2020) Human pluripotent stem cells-based therapies for neurodegenerative diseases: current status and challenges. Cells 9(11):2517

11.

Cai CY, Meng FL, Rao L, Liu YY, Zhao XL (2020) Induced pluripotent stem cell technology and its application in disease research. Yi Chuan 42(11):1042–1061PubMed

12.

Reddy AP, Ravichandran J (1866) Carkaci-Salli N (2020) Neural regeneration therapies for Alzheimer’s and Parkinson’s disease-related disorders. Biochim Biophys Acta Mol Basis Dis 4:165506

13.

Hayashi Y, Ohnuma K, Furue MK (2019) Pluripotent stem cell heterogeneity. Adv Exp Med Biol 1123:71–94PubMedCrossRef

14.

Chang CY, Ting HC, Liu CA, Su HL, Chiou TW, Lin SZ, Harn HJ, Ho TJ (2020) Induced pluripotent stem cell (iPSC)-based neurodegenerative disease models for phenotype recapitulation and drug screening. Molecules 25(8):2000

15.

Parmar M (2018) Towards stem cell based therapies for Parkinson’s disease. Development 145(1):dev156117

16.

Xu X, Huang J, Li J, Liu L, Han C, Shen Y, Zhang G, Jiang H, Lin Z, Xiong N et al (2016) Induced pluripotent stem cells and Parkinson’s disease: modelling and treatment. Cell Prolif 49(1):14–26PubMedPubMedCentralCrossRef

17.

Shahbazi E, Mirakhori F, Ezzatizadeh V, Baharvand H (2018) Reprogramming of somatic cells to induced neural stem cells. Methods 133:21–28PubMedCrossRef

18.

Monni E, Cusulin C, Cavallaro M, Lindvall O, Kokaia Z (2014) Human fetal striatum-derived neural stem (NS) cells differentiate to mature neurons in vitro and in vivo. Curr Stem Cell Res Ther 9(4):338–346PubMedCrossRef

19.

Choi DH, Kim JH, Kim SM, Kang K, Han DW, Lee J (2017) Therapeutic potential of induced neural stem cells for Parkinson’s disease. Int J Mol Sci 18(1):224PubMedPubMedCentralCrossRef

20.

Xu Z, Su S, Zhou S, Yang W, Deng X, Sun Y, Li L, Li Y (2020) How to reprogram human fibroblasts to neurons. Cell Biosci 10:116PubMedPubMedCentralCrossRef

21.

Wang H, Yang Y, Liu J, Qian L (2021) Direct cell reprogramming: approaches, mechanisms and progress. Nat Rev Mol Cell Biol 22(6):410–424PubMedPubMedCentralCrossRef

22.

Pfisterer U, Kirkeby A, Torper O, Wood J, Nelander J, Dufour A, Björklund A, Lindvall O, Jakobsson J, Parmar M (2011) Direct conversion of human fibroblasts to dopaminergic neurons. Proc Natl Acad Sci 108(25):10343–10348ADSPubMedPubMedCentralCrossRef

23.

Caiazzo M, Dell'Anno MT, Dvoretskova E, Lazarevic D, Taverna S, Leo D, Sotnikova TD, Menegon A, Roncaglia P, Colciago G et al (2011) Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 476(7359):224–227ADSPubMedCrossRef

24.

Kim J, Su SC, Wang H, Cheng AW, Cassady JP, Lodato MA, Lengner CJ, Chung CY, Dawlaty MM, Tsai LH et al (2011) Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell 9(5):413–419PubMedPubMedCentralCrossRef

25.

Dell'Anno MT, Caiazzo M, Leo D, Dvoretskova E, Medrihan L, Colasante G, Giannelli S, Theka I, Russo G, Mus L et al (2014) Remote control of induced dopaminergic neurons in parkinsonian rats. J Clin Invest 124(7):3215–3229PubMedPubMedCentralCrossRef

26.

Oh SI, Park HS, Hwang I, Park HK, Choi KA, Jeong H, Kim SW, Hong S (2014) Efficient reprogramming of mouse fibroblasts to neuronal cells including dopaminergic neurons. Sci World J 2014:957548CrossRef

27.

Tian C, Li Y, Huang Y, Wang Y, Chen D, Liu J, Deng X, Sun L, Anderson K, Qi X et al (2015) Selective generation of dopaminergic precursors from mouse fibroblasts by direct lineage conversion. Sci Rep 5:12622ADSPubMedPubMedCentralCrossRef

28.

Wang Y, Yang H, Yang Q, Yang J, Wang H, Xu H, Gao WQ (2016) Chemical conversion of mouse fibroblasts into functional dopaminergic neurons. Exp Cell Res 347(2):283–292PubMedCrossRef

29.

Qin H, Zhao AD, Sun ML, Ma K, Fu XB (2020) Direct conversion of human fibroblasts into dopaminergic neuron-like cells using small molecules and protein factors. Mil Med Res 7(1):52PubMedPubMedCentral

30.

Pereira M, Pfisterer U, Rylander D, Torper O, Lau S, Lundblad M, Grealish S, Parmar M (2014) Highly efficient generation of induced neurons from human fibroblasts that survive transplantation into the adult rat brain. Sci Rep 4:6330ADSPubMedPubMedCentralCrossRef

31.

Jiang H, Xu Z, Zhong P, Ren Y, Liang G, Schilling HA, Hu Z, Zhang Y, Wang X, Chen S et al (2015) Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons. Nat Commun 6:10100ADSPubMedCrossRef

32.

di Val R, Cervo P, Romanov RA, Spigolon G, Masini D, Martín-Montañez E, Toledo EM, La Manno G, Feyder M, Pifl C, Ng YH et al (2017) Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson’s disease model. Nat Biotechnolo 35(5):444–452CrossRef

33.

De Gregorio R, Pulcrano S, De Sanctis C, Volpicelli F, Guatteo E, von Oerthel L, Latagliata EC, Esposito R, Piscitelli RM, Perrone-Capano C et al (2018) miR-34b/c regulates Wnt1 and enhances mesencephalic dopaminergic neuron differentiation. Stem Cell Rep 10(4):1237–1250CrossRef

34.

Pu J, Gao T, Zheng R, Fang Y, Ruan Y, Jin C, Shen T, Tian J, Zhang B (2020) Parkin mutation decreases neurite complexity and maturation in neurons derived from human fibroblasts. Brain Res Bull 159:9–15PubMedCrossRef

35.

Zhou H, Su J, Hu X, Zhou C, Li H, Chen Z, Xiao Q, Wang B, Wu W, Sun Y et al (2020) Glia-to-neuron conversion by CRISPR-CasRx alleviates symptoms of neurological disease in mice. Cell 181(3):590–603.e516PubMedCrossRef

36.

Qian H, Kang X, Hu J, Zhang D, Liang Z, Meng F, Zhang X, Xue Y, Maimon R, Dowdy SF et al (2020) Reversing a model of Parkinson’s disease with in situ converted nigral neurons. Nature 582(7813):550–556ADSPubMedPubMedCentralCrossRef

37.

Yoo J, Noh M, Kim H, Jeon NL, Kim BS, Kim J (2015) Nanogrooved substrate promotes direct lineage reprogramming of fibroblasts to functional induced dopaminergic neurons. Biomaterials 45:36–45PubMedCrossRef

38.

Yoo J, Lee E, Kim HY, Youn DH, Jung J, Kim H, Chang Y, Lee W, Shin J, Baek S et al (2017) Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson’s disease therapy. Nat Nanotechnolo 12(10):1006–1014ADSCrossRef

39.

Chang JH, Tsai PH, Wang KY, Wei YT, Chiou SH, Mou CY (2018) Generation of functional dopaminergic neurons from reprogramming fibroblasts by nonviral-based mesoporous silica nanoparticles. Sci Rep 8(1):11ADSPubMedPubMedCentralCrossRef

40.

Chen Y, Pu J, Zhang B (2016) Progress and challenges of cell replacement therapy for neurodegenerative diseases based on direct neural reprogramming. Hum Gene ther 27(12):962–970PubMedCrossRef

41.

Diener C, Keller A, Meese E (2022) Emerging concepts of miRNA therapeutics: from cells to clinic. Trends Genet 38(6):613–626PubMedCrossRef

42.

Titze-de-Almeida SS, Soto-Sánchez C, Fernandez E, Koprich JB, Brotchie JM, Titze-de-Almeida R (2020) The promise and challenges of developing miRNA-based therapeutics for Parkinson’s disease. Cells 9(4):841PubMedPubMedCentralCrossRef

43.

Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, Ding S (2011) Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9(2):113–118PubMedPubMedCentralCrossRef

44.

Grealish S, Drouin-Ouellet J, Parmar M (2016) Brain repair and reprogramming: the route to clinical translation. J Intern Med 280(3):265–275PubMedCrossRef

45.

Wang Q, Liu Y, Han C, Yang M, Huang F, Duan X, Wang S, Yu Y, Liu J, Yang H et al (2021) Efficient RNA virus targeting via CRISPR/CasRx in fish. J Virol 95(19):e0046121PubMedCrossRef

46.

Chuang YF, Wang PY, Kumar S, Lama S, Lin FL, Liu GS (2021) Methods for in vitro CRISPR/CasRx-mediated RNA editing. Front Cell Dev Biol 9:667879PubMedPubMedCentralCrossRef

47.

Konermann S, Lotfy P, Brideau NJ, Oki J, Shokhirev MN, Hsu PD (2018) Transcriptome engineering with RNA-targeting type VI-D CRISPR effectors. Cell 173(3):665–676.e614PubMedPubMedCentralCrossRef

48.

Wang LL, Serrano C, Zhong X, Ma S, Zou Y, Zhang CL (2021) Revisiting astrocyte to neuron conversion with lineage tracing in vivo. Cell 184(21):5465–5481.e5416PubMedPubMedCentralCrossRef

49.

Mertens J, Marchetto MC, Bardy C, Gage FH (2016) Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience. Nat Rev Neurosci 17(7):424–437PubMedPubMedCentralCrossRef

50.

Arenas E, Denham M, Villaescusa JC (2015) How to make a midbrain dopaminergic neuron. Development 142(11):1918–1936PubMedCrossRef

51.

Playne R, Connor B (2017) Understanding Parkinson’s disease through the use of cell reprogramming. Stem Cell Rev Rep 13(2):151–169PubMedCrossRef

Title: Progress in direct reprogramming of dopaminergic cell replacement therapy
Authors: Yuan Yuan Zheng
Hui Xu
Yue Si Wang
Publication date: 10-11-2023
Publisher: Springer International Publishing
Keyword: Parkinson's Disease
Published in: Neurological Sciences / Issue 3/2024
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-023-07175-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Progress in direct reprogramming of dopaminergic cell replacement therapy

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2024

Pharmacological treatment of Tourette’s syndrome: from the past to the future

Parkinsonism with prominent neuropsychiatric symptoms without pyramidal involvement in a patient with FBXO7 variants

Isolated pontocerebellar leukoencephalopathy in HIV-related PML: focus on the “shrimp sign”

Profiling migraine patients according to clinical and psychophysical characteristics: clinical validity of distinct migraine clusters

Retraction Note: Pallidal deep brain stimulation for tardive dystonia: meta-analysis of clinical outcomes

User appraisal of a booklet for advance care planning in multiple sclerosis: a multicenter, qualitative Italian study