Chromosomal aberrations and deoxyribonucleic acid single-strand breaks in adipose-derived stem cells during long-term expansion in vitro

Froelich, Katrin; Mickler, Johannes; Steusloff, Gudrun; Technau, Antje; Tirado, Mario Ramos; Scherzed, Agmal; Hackenberg, Stephan; Radeloff, Andreas; Hagen, Rudolf; Kleinsasser, Norbert

doi:10.1016/j.jcyt.2012.12.009

Cited by 56 publications

(47 citation statements)

References 97 publications

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“…The comparison of the tail length data from the present experiment and the study by Froelich et al (2013) showed an increase of 139.14-fold in the second passage. That result raises questions about the protocols used; the protocol with pH >13 that was used in the present study should be a more sensitive assay than those using a buffer at pH ≅ 10.…”

Section: Discussionsupporting

confidence: 61%

“…Furthermore, the origin of the cells must be considered because adipose tissue cells from rabbits were used in the present study, while the other researchers used human cells. Moreover, Froelich et al (2013) indicated the absence of genotoxicity in longterm cultures. However, they found an increased frequency of mutagenic damage and inferred the possibility of transformation of the MSCs into cells with chromosomal instability and/or malignant potential.…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries

et al. 2014

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ABSTRACT. Rupture of the Achilles tendon diminishes quality of life. The gold-standard therapy is a surgical suture, but this presents complications, including wound formation and inflammation. These complications spurred evaluation of the therapeutic potential of 10435 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (4): 10434-10449 (2014) Stem cells for tendon injury treatment mesenchymal stem cells (MSCs) from adipose tissue. New Zealand rabbits were divided into 6 groups (three treatments with two time points each) evaluated at either 14 or 28 days after surgery: cross section of the Achilles tendon (CSAT); CSAT + Suture; and CSAT + MSC. A comparison between all groups at both time points showed a statistically significant increase in capillaries and in the structural organization of collagen in the healed tendon in the CSAT + Suture and CSAT + MSC groups at the 14-day assessment. Comparison between the two time points within the same group showed a statistically significant decrease in the inflammatory process and an increase in the structural organization of collagen in the CSAT and CSAT + MSC groups. A study of the genomic integrity of the cells suggested a linear correlation between an increase of injuries and culture time. Thus, MSC transplantation is a good alternative for treatment of Achilles tendon ruptures because it may be conducted without surgery and tendon suture and, therefore, has no risk of adverse effects resulting from the surgical wound or inflammation caused by nonabsorbable sutures. Furthermore, this alternative treatment exhibits a better capacity for wound healing and maintaining the original tendon architecture, depending on the arrangement of the collagen fibers, and has important therapeutic potential.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries

et al. 2014

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“…They suggested using caution with cell therapy, considering that the number of passages is directly proportional to the exposure time of the MSC clonal expansion process. Froelich et al (2013) performed in vitro expansion of MSCs over ten passages and the cells from passages 1, 2, 3, 5, and 10 were used for the comet assay in a pH > 13 alkaline version. They asserted that there was no directly proportional relationship between the damage levels and the comet assay passages; in others words, the increase of damage in the clonal expansion length.…”

Section: Discussionmentioning

confidence: 99%

“…However, unlike the aforementioned authors, Fuchs et al (2012), using the pH > 13 comet assay version, obtained results in which the increase in the number of passages coincided with increased frequency of DNA damage. Froelich et al (2013) also detected chromosomal aberrations by means of the chromosomal aberration test, even when the comet assay did not detect damage. This same finding is also reported by Nikitina et al (2011) andBochkov et al (2006).…”

Section: Discussionmentioning

confidence: 99%

“…Although a large number of stem cells can be isolated from adipose tissue, in vitro cell expansion is still required (Mesimäki et al, 2009), as the procedures require millions of cells. However, clonal expansion concerns the scientific community because the current literature includes studies in which authors have reported an increased risk of genetic instability, spontaneous transformation, and formation of in vivo malignant tumors (Froelich et al, 2013). Such reports raise the need for further studies in order to ensure the safety of cell therapy methods that are also more efficient, reliable, and sensitive for the detection of genomic damage in stem cells.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of pH effects on genomic integrity in adipose-derived mesenchymal stem cells using the comet assay

et al. 2015

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ABSTRACT. The use of mesenchymal stem cells (MSCs) in experimental, clinical, and therapeutic trials has grown in recent years. However, the issue remains of whether these procedures are completely safe for transplant patients. Therefore, this study was designed and carried out with the aim of evaluating two different comet assay protocols for genomic damage pattern analysis in MSCs derived from adipose tissue. The analyzed and interpreted results suggest that genetic testing is needed to support clonal expansion safety in cell therapy procedures with MSCs. Furthermore, they also suggest that if the comet assay technique would be used as a genomic integrity screening assay, the protocol performed at pH = 12 (that yielded a frequency of damaged cells: tail intensity = 9.50 ± 0.60, tail moment = 0.0122 ± 0.0007; results are reported as means ± standard deviation) would be indicated as genomic damage, and that subsequent single-strand breaks occur at pH > 13 (frequency of damaged cells: tail intensity = 30.71 ± 4.23, tail moment = 0.0447 ± 0.0073). Our study demonstrates that, in the era of regenerative medicine, it is necessary to standardize and establish a battery of tests in order to identify genomic damage prior to MSC transplantation.

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Biological changes in human mesenchymal stromal cells during monolayer culture

Herrmann

Bara

2016

The Biology and Therapeutic Application of Mesenchymal Cells

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Chromosomal aberrations and deoxyribonucleic acid single-strand breaks in adipose-derived stem cells during long-term expansion in vitro

Cited by 56 publications

References 97 publications

Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries

Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries

Evaluation of pH effects on genomic integrity in adipose-derived mesenchymal stem cells using the comet assay

Biological changes in human mesenchymal stromal cells during monolayer culture

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