Immortalization Reversibility in the Context of Cell Therapy Biosafety

Immortalization (genetically induced prevention of replicative senescence) is a promising approach to obtain cellular material for cell therapy or for bio-artificial organs aimed at overcoming the problem of donor material shortage. Immortalization is reversed before cells are used in vivo to allow...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-04, Vol.24 (9), p.7738
Main Authors: Sutyagina, Oksana I, Beilin, Arkadii K, Vorotelyak, Ekaterina A, Vasiliev, Andrey V
Format: Article
Language:English
Subjects:
Artificial chromosomes
Artificial organs
Biological products
Biosafety
c-MycERTAM
Cell cycle
Cell Differentiation
Cell division
Cell Line
Cell lines
Cell Proliferation
Cell therapy
Containment of Biohazards
CRISPR
Differentiation (biology)
Donor materials
Extracellular matrix
Genotype & phenotype
hTERT
Human papillomavirus
Immortalization
Insulin
Liu, Timothy
Phenotypes
Proteins
Recombination
reversible immortalization
Review
Safety and security measures
Senescence
site-specific-recombination
Stem cells
Suicide
Suicide genes
SV40T
Telomerase
Telomerase - metabolism
Tet-On/Tet-Off system
Tetracycline
Tetracyclines
Tissue engineering
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Summary:Immortalization (genetically induced prevention of replicative senescence) is a promising approach to obtain cellular material for cell therapy or for bio-artificial organs aimed at overcoming the problem of donor material shortage. Immortalization is reversed before cells are used in vivo to allow cell differentiation into the mature phenotype and avoid tumorigenic effects of unlimited cell proliferation. However, there is no certainty that the process of de-immortalization is 100% effective and that it does not cause unwanted changes in the cell. In this review, we discuss various approaches to reversible immortalization, emphasizing their advantages and disadvantages in terms of biosafety. We describe the most promising approaches in improving the biosafety of reversibly immortalized cells: CRISPR/Cas9-mediated immortogene insertion, tamoxifen-mediated self-recombination, tools for selection of successfully immortalized cells, using a decellularized extracellular matrix, and ensuring post-transplant safety with the use of suicide genes. The last process may be used as an add-on for previously existing reversible immortalized cell lines.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24097738