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Journal of Translational Medicine

, 12:95

Cell, tissue and gene therapy

Abstract

BackgroundIn osteosarcoma OS and most Ewing sarcoma EWS patients, the primary tumor originates in the bone. Although tumor resection surgery is commonly used to treat these diseases, it frequently leaves massive bone defects that are particularly difficult to be treated. Due to the therapeutic potential of mesenchymal stem cells MSCs, OS and EWS patients could benefit from an autologous MSCs-based bone reconstruction. However, safety concerns regarding the in vitro expansion of bone marrow-derived MSCs have been raised. To investigate the possible oncogenic potential of MSCs from OS or EWS patients MSC-SAR after expansion, this study focused on a biosafety assessment of MSC-SAR obtained after short- and long-term cultivation compared with MSCs from healthy donors MSC-CTRL.

MethodsWe initially characterized the morphology, immunophenotype, and differentiation multipotency of isolated MSC-SAR. MSC-SAR and MSC-CTRL were subsequently expanded under identical culture conditions. Cells at the early P3-P4 and late P10 passages were collected for the in vitro analyses including: sequencing of genes frequently mutated in OS and EWS, evaluation of telomerase activity, assessment of the gene expression profile and activity of major cancer pathways, cytogenetic analysis on synchronous MSCs, and molecular karyotyping using a comparative genomic hybridization CGH array.

ResultsMSC-SAR displayed comparable morphology, immunophenotype, proliferation rate, differentiation potential, and telomerase activity to MSC-CTRL. Both cell types displayed signs of senescence in the late stages of culture with no relevant changes in cancer gene expression. However, cytogenetic analysis detected chromosomal anomalies in the early and late stages of MSC-SAR and MSC-CTRL after culture.

ConclusionsOur results demonstrated that the in vitro expansion of MSCs does not influence or favor malignant transformation since MSC-SAR were not more prone than MSC-CTRL to deleterious changes during culture. However, the presence of chromosomal aberrations supports rigorous phenotypic, functional and genetic evaluation of the biosafety of MSCs, which is important for clinical applications.

KeywordsEwing sarcoma EWS Mesenchymal stem cells MSCs Osteosarcoma OS Tissue regeneration Tumorigenic transformation AbbreviationsBMBone marrow

EWSEwing sarcoma

MSCsMesenchymal stem cells

MSC-SARMSCs from BM sarcoma patients

MSC-CTRLMSCs from BM healthy patients

OSOsteosarcoma.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-12-95 contains supplementary material, which is available to authorized users.

Enrico Lucarelli, Chiara Bellotti contributed equally to this work.

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Author: Enrico Lucarelli - Chiara Bellotti - Melissa Mantelli - Maria Antonietta Avanzini - Rita Maccario - Francesca Novara - Giul

Source: https://link.springer.com/







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