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Assessment of Risks and Benefits of Using Antibiotics Resistance Genes in Mesenchymal Stem Cell-Based Ex-Vivo Therapy.
- Source :
-
International journal of stem cells [Int J Stem Cells] 2023 Nov 30; Vol. 16 (4), pp. 438-447. Date of Electronic Publication: 2023 Jun 30. - Publication Year :
- 2023
-
Abstract
- Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro . Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene ( PuroR ) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo , we generated a puromycin-resistant E. coli ( E. coli / PuroR ) by introducing the PuroR gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the PuroR gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, E. coli / PuroR . In summary, our study highlights the potential benefits of using the PuroR gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes in vivo can be effectively managed by clinically available antibiotics.
Details
- Language :
- English
- ISSN :
- 2005-3606
- Volume :
- 16
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of stem cells
- Publication Type :
- Academic Journal
- Accession number :
- 37385638
- Full Text :
- https://doi.org/10.15283/ijsc23053