Renjian Lu

doi:10.70711/mhr.v2i5.6278

Current Status and Progress of Cell Replacement Therapy for Parkinsons Disease

Renjian Lu

Abstract

Parkinsons disease (PD), the second most prevalent neurodegenerative disorder globally, is characterized by the degeneration and
death of dopaminergic neurons in the substantia nigra, leading to a range of motor and non-motor symptoms. Existing clinical treatments have
many limitations, and cell replacement therapy offers new hope for PD treatment. This article systematically summarizes the current status
and progress of cell replacement therapy for Parkinsons disease, covering strategies such as cell transplantation and in vivo direct reprogramming and discusses future directions, aiming to provide a comprehensive reference for PD therapeutic research.

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References

[1] Dorsey E R, Sherer T, Okun M S, et al. The emerging evidence of the parkinson pandemic[J]. J Parkinsons Dis, 2018, 8(s1): S3-S8.

[2] Morris H R, Spillantini M G, Sue C M, et al. The pathogenesis of Parkinson's disease[J]. Lancet, 2024, 403(10423):293-304.

[3] Postuma R B, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease[J]. Mov Disord, 2015, 30(12): 1591 -

1601.

[4] Chen W, Xiao Q, Shao M, et al. Prevalence of wearing - off and dyskinesia among the patients with Parkinson's disease on levodopa

therapy: A multi - center registry survey in China's mainland[J]. Transl Neurodegener, 2014, 3(1):26.

[5] Skidmore S, Barker R A. Challenges in the clinical advancement of cell therapies for Parkinson's disease[J]. Nat Biomed Eng, 2023,

7(4):370-386.

[6] Barker R A, Drouin - Ouellet J, Parmar M. Cell - based therapies for Parkinson disease: Past insights and future potential[J]. Nat Rev

Neurol, 2015, 11(9):492-503.

[7] Lindvall O, Brundin P, Widner H, et al. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease[J].

Science, 1990, 247(4942): 574 - 577.

[8] Parmar M, Grealish S, Henchcliffe C. The future of stem cell therapies for Parkinson disease[J]. Nat Rev Neurosci, 2020, 21(2): 103 - 115.

[9] Freed C R, Greene P E, Breeze R E, et al. Transplantation of embryonic dopamine neurons for severe Parkinson's disease[J]. N Engl J

Med, 2001, 344(10): 710 - 719

[10] Perrier A L, Tabar V, Barberi T, et al. Derivation of midbrain dopamine neurons from human embryonic stem cells[J]. Proc Natl Acad

Sci USA, 2004, 101(34): 12543 - 12548.

[11] Kriks S, Shim J, Piao J, et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's

disease[J]. Nature, 2011, 480(7378): 547 - 551.

[12] BlueRock Therapeutics LP. BlueRock Therapeutics investigational cell therapy bemdaneprocel for Parkinsons disease shows positive

data at 24 - months - [Z]. 2024, 24 - 28, 2024.

[13] Kirkeby A, Nelander J, Hoban D B, et al. Preclinical quality, safety, and efficacy of a human embryonic stem cell - derived product for

the treatment of Parkinson's disease, STEM - PD[J]. Cell Stem Cell, 2023, 30(10): 1299 - 1314.

[14] Wernig M, Zhao J, Pruszak J, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease[J]. Proc Natl Acad Sci USA, 2008, 105(15): 5856 - 5861.

[15] Schweitzer J S, Song B, Herrington T M, et al. Personalized iPSC - derived dopamine progenitor cells for Parkinson s disease[J]. N

Engl J Med, 2020, 382(20): 1926 - 1932.

[16] DOI D, Magotani H, Kikuchi T, et al. Pre - clinical study of induced pluripotent stem cell - derived dopaminergic progenitor cells for

Parkinson's disease[J]. Nat Commun, 2020, 11(1): 3369.

[17] Hiller B M, Marmion D J, Thompson C A, et al. Optimizing maturity and dose of iPSC - derived dopamine progenitor cell therapy for

Parkinson's disease[J]. NPJ Regen Med, 2022, 7(1): 24.

[18] Niu W, Zang T, Zou Y, et al. In vivo reprogramming of astrocytes to neuroblasts in the adult brain[J]. Nat Cell Biol, 2013, 15(10): 1164 -

1175.

[19] Guo Z, Zhang L, Wu Z, et al. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an

Alzheimer's disease model[J]. Cell Stem Cell, 2014, 14(2): 188 - 202.

[20] Caiazzo M, Dell'Anno M T, Dvoretskova E, et al. Direct generation of functional dopaminergic neurons from mouse and human

fibroblasts[J]. Nature, 2011, 476(7359): 224 - 227.

[21] Addis R C, HSU F, Wright R L, et al. Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single

polycistronic vector[J]. PLoS One, 2011, 6(12): e28719.

[22] Torper O, Ottosson D R, Pereira M, et al. In vivo reprogramming of striatal NG2 glia into functional neurons that integrate into local

host circuitry[J]. Cell Rep, 2015, 12(3): 474 - 481.

[23] Pereira M, Birtele M, Shrigley S, et al. Direct reprogramming of resident NG2 glia into neurons with properties of fast - spiking parvalbumin - containing interneurons[J]. Stem Cell Reports, 2017, 9(3): 742 - 751.

[24] Rivetti di Val Cervo P, Romanov R A, Spigolon G, et al. Induction of functional dopamine neurons from human astrocytes in vitro and

mouse astrocytes in a Parkinson's disease model[J]. Nat Biotechnol, 2017, 35(5): 444 - 452.

[25] Niu W, Zang T, Wang L, et al. Phenotypic reprogramming of striatal neurons into dopaminergic neuron - like cells in the adult mouse

brain[J]. Stem Cell Reports, 2018, 11(5): 1156 - 1170.

[26] Skidmore S, Barker R A. Challenges in the clinical advancement of cell therapies for Parkinson's disease[J]. Nat Biomed Eng, 2023,

7(4): 370-386.

[27] Wang Bin, Li Zegui. Strategies and Clinical Application Progress of Embryonic Stem Cell Transplantation for Parkinson's Disease. Chinese Journal of Neurology. 2009; 42(05).

[28] Park T, Jeon J, Lee N, et al. Co-transplantation of autologous Treg cells in a cell therapy for Parkinson's disease[J]. Nature, 2023,

619(7970): 606-615.

[29] Parmar M, Grealish S, Henchcliffe C. The future of stem cell therapies for Parkinson disease[J]. Nat Rev Neurosci, 2020, 21(2): 103-

115.

[30] Yoo J, Lee E, Kim H Y, et al. Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson's disease therapy[J]. Nat Nanotechnol, 2017, 12(10): 1006 - 1014.

DOI: http://dx.doi.org/10.70711/mhr.v2i5.6278

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