Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2020 Nov 25

PMID 33233861

Citations 28

Authors

Elizabeth Ford

Jodie Pearlman

Travis Ruan

John Manion

Matthew Waller

Gregory G Neely

Leslie Caron

Affiliations

Soon will be listed here.

Abstract

Neurodegenerative diseases are characterized by irreversible cell damage, loss of neuronal cells and limited regeneration potential of the adult nervous system. Pluripotent stem cells are capable of differentiating into the multitude of cell types that compose the central and peripheral nervous systems and so have become the major focus of cell replacement therapies for the treatment of neurological disorders. Human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC)-derived cells have both been extensively studied as cell therapies in a wide range of neurodegenerative disease models in rodents and non-human primates, including Parkinson's disease, stroke, epilepsy, spinal cord injury, Alzheimer's disease, multiple sclerosis and pain. In this review, we discuss the latest progress made with stem cell therapies targeting these pathologies. We also evaluate the challenges in clinical application of human pluripotent stem cell (hPSC)-based therapies including risk of oncogenesis and tumor formation, immune rejection and difficulty in regeneration of the heterogeneous cell types composing the central nervous system.

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References

Nie Z, Hu G, Wei G, Cui K, Yamane A, Resch W . c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells. Cell. 2012; 151(1):68-79. PMC: 3471363. DOI: 10.1016/j.cell.2012.08.033. View

Stirling D, Khodarahmi K, Liu J, McPhail L, McBride C, Steeves J . Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. J Neurosci. 2004; 24(9):2182-90. PMC: 6730425. DOI: 10.1523/JNEUROSCI.5275-03.2004. View

All A, Gharibani P, Gupta S, Bazley F, Pashai N, Chou B . Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors. PLoS One. 2015; 10(1):e0116933. PMC: 4311989. DOI: 10.1371/journal.pone.0116933. View

Woltjen K, Michael I, Mohseni P, Desai R, Mileikovsky M, Hamalainen R . piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature. 2009; 458(7239):766-70. PMC: 3758996. DOI: 10.1038/nature07863. View

Schwartz S, Hubschman J, Heilwell G, Franco-Cardenas V, Pan C, Ostrick R . Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012; 379(9817):713-20. DOI: 10.1016/S0140-6736(12)60028-2. View

Yamakado H, Moriwaki Y, Yamasaki N, Miyakawa T, Kurisu J, Uemura K . α-Synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior and hyperlocomotion. Neurosci Res. 2012; 73(2):173-7. DOI: 10.1016/j.neures.2012.03.010. View

Palla A, Piazzolla D, Alcazar N, Canamero M, Grana O, Gomez-Lopez G . The pluripotency factor NANOG promotes the formation of squamous cell carcinomas. Sci Rep. 2015; 5:10205. PMC: 4437308. DOI: 10.1038/srep10205. View

Palma-Tortosa S, Tornero D, Hansen M, Monni E, Hajy M, Kartsivadze S . Activity in grafted human iPS cell-derived cortical neurons integrated in stroke-injured rat brain regulates motor behavior. Proc Natl Acad Sci U S A. 2020; 117(16):9094-9100. PMC: 7183146. DOI: 10.1073/pnas.2000690117. View

Somay C, Grunt T, Mannhalter C, Dittrich C . Relationship of myc protein expression to the phenotype and to the growth potential of HOC-7 ovarian cancer cells. Br J Cancer. 1992; 66(1):93-8. PMC: 1977897. DOI: 10.1038/bjc.1992.223. View

10.

Li L, Baroja M, Majumdar A, Chadwick K, Rouleau A, Gallacher L . Human embryonic stem cells possess immune-privileged properties. Stem Cells. 2004; 22(4):448-56. DOI: 10.1634/stemcells.22-4-448. View

11.

Figge D, Eskow Jaunarajs K, Standaert D . Dynamic DNA Methylation Regulates Levodopa-Induced Dyskinesia. J Neurosci. 2016; 36(24):6514-24. PMC: 5015786. DOI: 10.1523/JNEUROSCI.0683-16.2016. View

12.

Chang Y, Chu T, Ding D . WNT/β-Catenin signaling pathway regulates non-tumorigenesis of human embryonic stem cells co-cultured with human umbilical cord mesenchymal stem cells. Sci Rep. 2017; 7:41913. PMC: 5291217. DOI: 10.1038/srep41913. View

13.

Stirling D, Cummins K, Mishra M, Teo W, Yong V, Stys P . Toll-like receptor 2-mediated alternative activation of microglia is protective after spinal cord injury. Brain. 2013; 137(Pt 3):707-23. DOI: 10.1093/brain/awt341. View

14.

Merkle F, Ghosh S, Kamitaki N, Mitchell J, Avior Y, Mello C . Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature. 2017; 545(7653):229-233. PMC: 5427175. DOI: 10.1038/nature22312. View

15.

Li S, Wu X, Dong C, Xie X, Wu J, Zhang X . The differential expression of OCT4 isoforms in cervical carcinoma. PLoS One. 2015; 10(3):e0118033. PMC: 4376746. DOI: 10.1371/journal.pone.0118033. View

16.

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

17.

Liang Q, Monetti C, Shutova M, Neely E, Hacibekiroglu S, Yang H . Linking a cell-division gene and a suicide gene to define and improve cell therapy safety. Nature. 2018; 563(7733):701-704. DOI: 10.1038/s41586-018-0733-7. View

18.

Jang Y, Choi J, Park N, Kang J, Kim M, Kim Y . Development of immunocompatible pluripotent stem cells via CRISPR-based human leukocyte antigen engineering. Exp Mol Med. 2019; 51(1):1-11. PMC: 6323054. DOI: 10.1038/s12276-018-0190-2. View

19.

Yue W, Li Y, Zhang T, Jiang M, Qian Y, Zhang M . ESC-Derived Basal Forebrain Cholinergic Neurons Ameliorate the Cognitive Symptoms Associated with Alzheimer's Disease in Mouse Models. Stem Cell Reports. 2015; 5(5):776-790. PMC: 4649256. DOI: 10.1016/j.stemcr.2015.09.010. View

20.

Hermanto Y, Sunohara T, Faried A, Takagi Y, Takahashi J, Maki T . Transplantation of feeder-free human induced pluripotent stem cell-derived cortical neuron progenitors in adult male Wistar rats with focal brain ischemia. J Neurosci Res. 2017; 96(5):863-874. DOI: 10.1002/jnr.24197. View