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Emergence of clonal chromosomal alterations during the mesenchymal stromal cell cultivation

Overview of attention for article published in Molecular Cytogenetics, December 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#7 of 217)
  • High Attention Score compared to outputs of the same age (85th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

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1 blog
twitter
2 tweeters

Citations

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10 Dimensions

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34 Mendeley
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Title
Emergence of clonal chromosomal alterations during the mesenchymal stromal cell cultivation
Published in
Molecular Cytogenetics, December 2015
DOI 10.1186/s13039-015-0197-5
Pubmed ID
Authors

Tamara Borgonovo, Maria Marlene Solarewicz, Isadora May Vaz, Debora Daga, Carmen Lúcia Kuniyoshi Rebelatto, Alexandra Cristina Senegaglia, Enilze Ribeiro, Iglenir João Cavalli, Paulo Slud Brofman

Abstract

Use of human mesenchymal stromal cells (MSCs) is a promising strategy for cell therapy in injured tissues recovery. However, MSCs acquire genetic changes when cultivated in vitro that make them more susceptible to undergo neoplastic transformation. Therefore, genomic integrity of stem cells should be monitored carefully for the use in basic research and clinical trials, including karyotype analysis to confirm the absence of genetic instability. Here, we report a case of a male 67-year-old patient selected to join the study: "Autologous transplantation of mesenchymal cells for treatment of severe and refractory ischemic cardiomyopathy". He underwent nephrectomy for malignant tumor on the right kidney. Cytogenetic analysis on a bone marrow sample showed a normal karyotype: 46,XY[20]. However, the MSC at second passage showed a hyperdiploid clone, with clonal trisomies of chromosomes 4, 5, 10 and X. In order to investigate more, another sample from the same patient was used for a second cultivation and, at third passage, these cells showed a clonal translocation t(9;18)(p24;q11). The recurrent aberrations in MSC may indicate the beginning of a spontaneous transformation in culture, so, these cells were not used for cell therapy. Several analyses were performed at the Center for Cell Technology (152 samples), however this was the only case to show clonal cytogenetic abnormalities. Interestingly, two distinct clonal alterations were seen in two parallel cell cultivations from the same patient, suggesting a propensity for genetic instability. This highlights the need to evaluate these cells on a case-by-case basis, especially in patients with a history of cancer. Although there is controversy about the use of cells with cytogenetic abnormality for therapy, because their tumorigenic doubtful potential, we decided against the use of these cells for regenerative medicine. Here, we report a case of a male 67-year-old patient selected to join the study: "Autologous transplantation of mesenchymal cells for treatment of severe and refractory ischemic cardiomyopathy". He underwent nephrectomy for malignant tumor on the right kidney. Cytogenetic analysis on a bone marrow sample showed a normal karyotype: 46,XY[20]. However, the MSC at second passage showed a hyperdiploid clone, with clonal trisomies of chromosomes 4, 5, 10 and X. In order to investigate more, another sample from the same patient was used for a second cultivation and, at third passage, these cells showed a clonal translocation t(9;18)(p24;q11). The recurrent aberrations in MSC may indicate the beginning of a spontaneous transformation in culture, so, these cells were not used for cell therapy. Several analyses were performed at the Center for Cell Technology(152 samples), however this was the only case to show clonal cytogenetic abnormalities. Interestingly, two distinct clonal alterations were seen in two parallel cell cultivations from the same patient, suggesting a propensity for genetic instability. This highlights the need to evaluate these cells on a case-by-case basis, especially in patients with a history of cancer. Although there is controversy about the use of cells with cytogenetic abnormality for therapy, because their tumorigenic doubtful potential, we decided against the use of these cells forregenerative medicine.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 3%
United States 1 3%
Unknown 32 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 26%
Researcher 6 18%
Student > Bachelor 4 12%
Other 3 9%
Student > Master 3 9%
Other 7 21%
Unknown 2 6%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 29%
Medicine and Dentistry 10 29%
Agricultural and Biological Sciences 8 24%
Engineering 2 6%
Unspecified 1 3%
Other 2 6%
Unknown 1 3%

Attention Score in Context

This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 February 2016.
All research outputs
#810,645
of 7,206,148 outputs
Outputs from Molecular Cytogenetics
#7
of 217 outputs
Outputs of similar age
#43,203
of 289,663 outputs
Outputs of similar age from Molecular Cytogenetics
#1
of 37 outputs
Altmetric has tracked 7,206,148 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 217 research outputs from this source. They receive a mean Attention Score of 1.7. This one has done particularly well, scoring higher than 96% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 289,663 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.