Human Bone Marrow–Derived Mesenchymal Stem Cells Do Not Undergo Transformation after Long-term<i>In vitro</i>Culture and Do Not Exhibit Telomere Maintenance Mechanisms

Cancer Research - Tập 67 Số 19 - Trang 9142-9149 - 2007
Maria Ester Bernardo1, Nadia Zaffaroni2, Francesca Novara3, Angela Cometa1, Maria Antonietta Avanzini1, Antonia Moretta1, Daniela Montagna1, Rita Maccario1, Raffaella Villa2, Maria Grazia Daidone2, Orsetta Zuffardi3, Franco Locatelli1
11Oncoematologia Pediatrica and
23Dipartimento di Oncologia Sperimentale, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy
32Biologia Generale e Genetica Medica, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Università di Pavia, Pavia, Italy; and

Tóm tắt

AbstractSignificant improvement in the understanding of mesenchymal stem cell (MSC) biology has opened the way to their clinical use. However, concerns regarding the possibility that MSCs undergo malignant transformation have been raised. We investigated the susceptibility to transformation of human bone marrow (BM)–derived MSCs at different in vitro culture time points. MSCs were isolated from BM of 10 healthy donors and propagated in vitro until reaching either senescence or passage (P) 25. MSCs in the senescence phase were closely monitored for 8 to 12 weeks before interrupting the cultures. The genetic characterization of MSCs was investigated through array-comparative genomic hybridization (array-CGH), conventional karyotyping, and subtelomeric fluorescent in situ hybridization analysis both before and after prolonged culture. MSCs were tested for the expression of telomerase activity, human telomerase reverse transcriptase (hTERT) transcripts, and alternative lengthening of telomere (ALT) mechanism at different passages. A huge variability in terms of proliferative capacity and MSCs life span was noted between donors. In eight of 10 donors, MSCs displayed a progressive decrease in proliferative capacity until reaching senescence. In the remaining two MSC samples, the cultures were interrupted at P25 to pursue data analysis. Array-CGH and cytogenetic analyses showed that MSCs expanded in vitro did not show chromosomal abnormalities. Telomerase activity and hTERT transcripts were not expressed in any of the examined cultures and telomeres shortened during the culture period. ALT was not evidenced in the MSCs tested. BM-derived MSCs can be safely expanded in vitro and are not susceptible to malignant transformation, thus rendering these cells suitable for cell therapy approaches. [Cancer Res 2007;67(19):9142–9]

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Cancer Research

Tập 67 Số 19

9142-9149

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