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Emergence of clonal chromosomal alterations during the mesenchymal stromal cell cultivation.

Borgonovo T, Solarewicz MM, Vaz IM, Daga D, Rebelatto CL, Senegaglia AC, Ribeiro E, Cavalli IJ, Brofman PS - Mol Cytogenet (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centro de Tecnologia Celular (CTC), Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná Brazil ; Cytogenetic Laboratory of Centro de Tecnololgia Celular (CTC), PUCPR, Curitiba, Brazil.

ABSTRACT

Background: 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.

Case presentation: 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus

Karyotype with translocation. Karyogram after cell expansion, from the second cultivation (mesenchymal stem cells at third passage). Karyotype: 46,XY, t(9;18)(p24;q11)
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Fig3: Karyotype with translocation. Karyogram after cell expansion, from the second cultivation (mesenchymal stem cells at third passage). Karyotype: 46,XY, t(9;18)(p24;q11)

Mentions: In order to investigate more, another sample of mononuclear cells (that had been frozen for backup) from the same patient, was used for a second cultivation. At P3, these cells showed a clonal translocation: 46,XY,t(9;18)(p24;q11)[8]/46,XY[5] (Fig. 3). At P5 the karyotype was 26 ~ 44,XY[10].Fig. 3


Emergence of clonal chromosomal alterations during the mesenchymal stromal cell cultivation.

Borgonovo T, Solarewicz MM, Vaz IM, Daga D, Rebelatto CL, Senegaglia AC, Ribeiro E, Cavalli IJ, Brofman PS - Mol Cytogenet (2015)

Karyotype with translocation. Karyogram after cell expansion, from the second cultivation (mesenchymal stem cells at third passage). Karyotype: 46,XY, t(9;18)(p24;q11)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666177&req=5

Fig3: Karyotype with translocation. Karyogram after cell expansion, from the second cultivation (mesenchymal stem cells at third passage). Karyotype: 46,XY, t(9;18)(p24;q11)
Mentions: In order to investigate more, another sample of mononuclear cells (that had been frozen for backup) from the same patient, was used for a second cultivation. At P3, these cells showed a clonal translocation: 46,XY,t(9;18)(p24;q11)[8]/46,XY[5] (Fig. 3). At P5 the karyotype was 26 ~ 44,XY[10].Fig. 3

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centro de Tecnologia Celular (CTC), Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná Brazil ; Cytogenetic Laboratory of Centro de Tecnololgia Celular (CTC), PUCPR, Curitiba, Brazil.

ABSTRACT

Background: 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.

Case presentation: 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus