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Buddingh EP, Ruslan SEN, Reijnders CMA, et al. Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture. Clin Sarcoma Res. 2015;5:16doi: 10.1186/s13569-015-0031-1.
Buddingh, E. P., Ruslan, S. E. N., Reijnders, C. M. A., Szuhai, K., Kuijjer, M. L., Roelofs, H., Hogendoorn, P. C. W., Maarten Egeler, R., Cleton-Jansen, A. M., & Lankester, A. C. (2015). Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture. Clinical sarcoma research, 516. https://doi.org/10.1186/s13569-015-0031-1
Buddingh, Emilie P, et al. "Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture." Clinical sarcoma research vol. 5 (2015): 16. doi: https://doi.org/10.1186/s13569-015-0031-1
Buddingh EP, Ruslan SEN, Reijnders CMA, Szuhai K, Kuijjer ML, Roelofs H, Hogendoorn PCW, Maarten Egeler R, Cleton-Jansen AM, Lankester AC. Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture. Clin Sarcoma Res. 2015 Jun 23;5:16. doi: 10.1186/s13569-015-0031-1. eCollection 2015. PMID: 26106474; PMCID: PMC4477606.
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Clin Sarcoma Res. 2015 Jun 23;5:16. doi: 10.1186/s13569-015-0031-1. eCollection 2015.

Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture.

Clinical sarcoma research

Emilie P Buddingh, S Eriaty N Ruslan, Christianne M A Reijnders, Karoly Szuhai, Marieke L Kuijjer, Helene Roelofs, Pancras C W Hogendoorn, R Maarten Egeler, Anne-Marie Cleton-Jansen, Arjan C Lankester

Affiliations

  1. Department of Pediatrics, J6-S, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
  2. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
  3. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
  4. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.

PMID: 26106474 PMCID: PMC4477606 DOI: 10.1186/s13569-015-0031-1

Abstract

BACKGROUND: In vitro expanded mesenchymal stromal cells (MSCs) are increasingly used as experimental cellular therapy. However, there have been concerns regarding the safety of their use, particularly with regard to possible oncogenic transformation. MSCs are the hypothesized precursor cells of high-grade osteosarcoma, a tumor with often complex karyotypes occurring mainly in adolescents and young adults.

METHODS: To determine if MSCs from osteosarcoma patients could be predisposed to malignant transformation we cultured MSCs of nine osteosarcoma patients and five healthy donors for an average of 649 days (range 601-679 days). Also, we compared MSCs derived from osteosarcoma patients at diagnosis and from healthy donors using genome wide gene expression profiling.

RESULTS: Upon increasing passage, increasing frequencies of binucleate cells were detected, but no increase in proliferation suggestive of malignant transformation occurred in MSCs from either patients or donors. Hematopoietic cell specific Lyn substrate 1 (HLCS1) was differentially expressed (fold change 0.25, P value 0.0005) between MSCs of osteosarcoma patients (n = 14) and healthy donors (n = 9).

CONCLUSIONS: This study shows that although HCLS1 expression was downregulated in MSCs of osteosarcoma patients and binucleate cells were present in both patient and donor derived MSCs, there was no evidence of neoplastic changes to occur during long-term culture.

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