Chromosome variability of human multipotent mesenchymal stromal cells

Бочков, Н. П.; Voronina, E. S.; Kosyakova, Nadezda; Liehr, Thomas; Rzhaninova, A. A.; Katosova, L. D.; Platonova, V. I.; Goldshtein, D. V.

doi:10.1007/s10517-007-0031-0

Cited by 36 publications

(39 citation statements)

References 9 publications

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“…Chromosomal aberration was found in late passages also by others (12,25). Therefore, our results support that ASC addressed to clinical use should be expanded only for few passages as well.…”

Section: Discussionsupporting

confidence: 84%

Analysis of the Karyotype of Expanded Human Adipose-Derived Stem Cells for Bone Reconstruction of the Maxillo-Facial Region

Bellotti

Stanco

Ragazzini

et al. 2013

Int J Immunopathol Pharmacol

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Mesenchymal stem cells (MSC) and adipose-derived stem cells (ASC) were recently proposed for bone maxillofacial reconstruction in association with biomaterials. For this application MSC must be ex-vivo expanded in order to obtain, for a given volume of implanted biomaterial, a relevant number of bone forming cells. Previously conducted pre-clinical studies suggested that a concentration of 6 x 10 8 ASC associated with 900 mg of anorganic bovine bone (ABB) could be effective for human maxillary sinus floor elevation. A keystone issue to guarantee the quality and safety of Advanced Therapy Medicinal Products containing expanded MSC and ASC is their chromosome stability in culture: this topic has been widely investigated and conflicting results have been published. Abnormal karyotype of human ex-vivo expanded MSC and ASC was found by some authors, while, at the same time, several other studies showed the MSC and ASC karyotype to be normal. It is therefore important that all the results obtained on MSC andASC karyotype analysis be published. Given this context, the aim of this manuscript, aim of this manuscript is to verify the karyotype stability of ASC in view oftheir applications in clinical trials. ASC obtained from the adipose tissue of 4 donors were expanded over extended culture time. Based on previous ASC expansions we hypothesized to be able to obtain 6 x lOS cells by passage 7. Karyotype analysis 000 metaphases was planned to be investigated at passage 2, 7, and 15 in all the cultures. No abnormalities were found in the karyotype of two donors at all the passages tested, while a translocation was found in 2 metaphases of a donor at passage 7, but not at passage 15, and in the fourth donor in 5 metaphases a trisomy was found at passage 15. Chromosomal abnormalities were detected only after extended ASC expansion. Whether these anomalies can be related to risk for the patient's safety will have to be demonstrated by in-vivo studies.

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Section: Discussionsupporting

confidence: 84%

Analysis of the Karyotype of Expanded Human Adipose-Derived Stem Cells for Bone Reconstruction of the Maxillo-Facial Region

Bellotti

Stanco

Ragazzini

et al. 2013

Int J Immunopathol Pharmacol

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“…All types of chromosome and genome mutations are detected in adult human SC cultures [1]. As the conditions of culturing and reinoculation of cell cultures are usually similar, the appearance of abnormal clones can be explained by their selective advantage in multiplication.…”

Section: Resultsmentioning

confidence: 99%

Aneuploidy of stem cells isolated from human adipose tissue

et al. 2008

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The incidence of autosomes 6 and 8 aneuploidy in stem cell cultures derived from adipose tissue was evaluated at different stages of culturing. Monosomy was more incident than trisomy during the early passages. Distribution of cultures by the incidence of aneuploidy in different chromosomes was virtually the same. Clones with chromosome 6 monosomy were detected in two cultures during late passages.

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“…Long-term culturing can lead to the appearance of cells with an abnormal karyotype, in addition to the selection of cells with a high proliferation rate. Therefore, cytogenetic stability and control are necessary for stem cells before transplantation to a donor organism (Bochkov et al 2007). We have shown that OC-RSCs not only maintain a high proliferative rate and purity after at least 8 passages, but also retain a normal diploid karyotype.…”

Section: Discussionmentioning

confidence: 99%

“…Chromosome preparations were made from the OC-RSCs at passage 8 and stained by conventional Giemsa staining as described by Bochkov et al (2007). In brief, colchicine (Sigma-Aldrich) at a final concentration of 0.01 µg/ml was added to flasks 1.5 h before fixation.…”

Section: Cytogenetic Analysismentioning

confidence: 99%

Characteristics of retinal stem cells from rat optic cup at embryonic day 12.5 (tailbud stage)

2008

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Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair of such damage by cell transplantation is one of the most feasible types of central nervous system treatment. Retinal stem cells (RSC) are a substrate for cell-replacement therapy, and previous studies have shown that RSCs from different developmental stages have distinct properties in proliferative capacity and differentiation potential. The tailbud stage is of special interest in retinogenesis, because RSCs commence differentiation after this period. However, no information about the characteristics of RSCs from the tailbud stage is available. In this study, the characteristics of cell cultures from the rat optic cup (referred to as optic-cup-derived RSCs; OC-RSCs) at embryonic day 12.5 (tailbud stage) were analyzed. OC-RSCs grew either as monolayers or as neurospheres in the presence of basic fibroblast growth factor and could be dissociated into a single cell suspension. Using the MTT assay, immunochemistry, cytogenetic analysis, and flow cytometry, we found that OC-RSCs were easily enriched to 92% by three passages, had a normal diploid karyotype, and exhibited no obvious differences in proliferative rate during eight passages (doubling time: 36 h). OC-RSCs produced retinal specific cells after the addition of serum to the medium, but the differentiation potential was affected by serum concentration. Preliminary results showed that transplanted OC-RSCs were incorporated into the degenerated retina of RCS rats and differentiated into rhodopsin-positive cells. Thus, OC-RSCs, after suitable enrichment, provide a population of stem cells with distinct growth and differentiation properties that make them suitable for research into RSC differentiation and transplantation.

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Chromosome variability of human multipotent mesenchymal stromal cells

Cited by 36 publications

References 9 publications

Analysis of the Karyotype of Expanded Human Adipose-Derived Stem Cells for Bone Reconstruction of the Maxillo-Facial Region

Analysis of the Karyotype of Expanded Human Adipose-Derived Stem Cells for Bone Reconstruction of the Maxillo-Facial Region

Aneuploidy of stem cells isolated from human adipose tissue

Characteristics of retinal stem cells from rat optic cup at embryonic day 12.5 (tailbud stage)

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