Risk of genetic transformation of multipotent mesenchymal stromal cells in vitro

Nikitina, V. A.; Chausheva, A. I.

doi:10.1134/s1022795413120077

Cited by 1 publication

(2 citation statements)

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“…However, similar to our results, the authors did not find a statistically significant difference between the initial and final (P20) passages (31). Similar results were described for Nikitina et al (39), who used the CA for analysis of human ADSC maintained in culture. The authors assessed DNA damage at early (3)(4) and late (10-12) passages.…”

Section: Discussionsupporting

confidence: 92%

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Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells

Malagutti-Ferreira

Crispim

Barufatti

et al. 2023

Braz J Med Biol Res

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Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.

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Section: Discussionsupporting

confidence: 92%

“…There was a statistically significant difference for passage 5, 7, 9, and 11 compared to the first and second passage (Table 2). The results obtained by Nikitina et al (39) using the MN were similar and showed an increase in apoptotic cells and number of micronuclei in the ADSC maintained in culture from the fourth passages onwards.…”

Section: Discussionsupporting

confidence: 60%