Osteogenic Progenitor Cell Potency After High-Dose Chemotherapy (COSS-96)

• Published in: Anticancer research 2005-03, Vol.25 (2A), p.947-954
• Main Authors: JÄGER, M, SCHULTHEIS, A, WESTHOFF, B, KRAUSPE, R
• Format: Article
• Language: English
• Subjects: Adolescent; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Neoplasms - drug therapy; Bone Neoplasms - pathology; Cartilage - cytology; Cartilage - drug effects; Cell Differentiation - drug effects; Cell Survival - drug effects; Chondroblastoma - drug therapy; Chondroblastoma - pathology; Cisplatin - administration & dosage; Cisplatin - adverse effects; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Female; Humans; Ifosfamide - administration & dosage; Ifosfamide - adverse effects; Medical sciences; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Methotrexate - administration & dosage; Methotrexate - adverse effects; Neoadjuvant Therapy; Osteosarcoma - drug therapy; Osteosarcoma - pathology; Periosteum - cytology; Periosteum - drug effects; Tumors; Tumors of striated muscle and skeleton
• ISSN: 0250-7005; 1791-7530

Background: Since the first trial of chemotherapy in patients with osteosarcoma the survival rate has gradually improved. For more than two decades, most osteosarcoma patients from Germany, Austria and Switzerland have been treated according to the protocols of the Cooperative Osteosarcoma Study Group (COSS). The uniform treatment concept of a high-dose polychemotherapy pre- and postoperatively improved the survival rate of these patients significantly. One severe side-effect of COSS chemotherapy is multiple osteonecrosis. Patients and Methods: In this study the osteogenic stem cell potency of three different tissue types was elucidated after COSS-96 chemotherapy (high-risk arm). Mononuclear cells were obtained from the periosteum, cartilage and bone marrow of a 17-year-old female with a chondroblastic osteosarcoma. The cells were cultivated for 4 weeks in standard medium and stimulated for osteogenic differentiation after the second passage with dexamethasone, glycerolphosphate and ascorbine acid. Two weeks later, the cell cultures were analysed with respect to cell morphology and immunochemical stainings. Results: All cells cultures showed an osteoblastic regeneration potential measured by osteocalcin (OC), osteopontin (OP) and alkaline phosphatase (ALP) expression. Compared to other donor tissues and localizations, the fibula periosteum showed siginificantly higher osteoblast rates in vitro, whereas collagen II, CD34 and CD45 were not expressed in any culture. Conclusion: The results of this study demonstrate the survival of mesenchymal progenitor cells in bone marrow during COSS-96 polychemotherapy, which allows for an osteogenic regeneration in vitro and potentially in vivo.