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Prog Brain Res. 2017;230:133-150. doi: 10.1016/bs.pbr.2017.02.007. Epub 2017 Apr 7.

Preparation, characterization, and banking of clinical-grade cells for neural transplantation: Scale up, fingerprinting, and genomic stability of stem cell lines.

Author information

1
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom; Translational Neurosurgery Group, Western General Hospital, Crewe Road South, Edinburgh, United Kingdom.
2
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom. Electronic address: tilo.kunath@ed.ac.uk.

Abstract

Parkinson's disease is a complex and progressive neurodegenerative condition that is characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate the striatum. Cell transplantation therapies to rebuild this dopaminergic network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as the source of cells for transplantation. However, reliance on terminations for a Parkinson's therapy presents significant logistical and ethical hurdles. An alternative source of transplantable mDA neurons is urgently needed, and the solution may come from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Protocols to differentiate hESCs/iPSCs toward mDA neurons are now robust and efficient, and upon grafting the cells rescue preclinical animal models of Parkinson's disease. The challenge now is to apply Good Manufacturing Practice (GMP) to the academic discoveries and protocols to produce clinical-grade transplantable mDA cells. Major technical and logistical considerations include (i) source of hESC or iPSC line, (ii) GMP compliance of the differentiation protocol and all reagents, (iii) characterization of the cell product in terms of identity, safety, and efficacy, (iv) characterization of genomic state and stability, and (v) banking of a transplantation-ready cell product. Approaches and solutions to these challenges are reviewed here.

KEYWORDS:

Cell transplantation; Cryopreservation; Good Manufacturing Practice; Human embryonic stem cells; Induced pluripotent stem cells; Midbrain dopaminergic neurons; Molecular karyotype; Parkinson's disease; Single nucleotide polymorphisms

PMID:
28552226
DOI:
10.1016/bs.pbr.2017.02.007
[Indexed for MEDLINE]

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