Osteogenic progenitor cell potency after high-dose chemotherapy (COSS-96).
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.


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 significantly higher osteoblast rates in vitro, whereas collagen II, CD34 and CD45 were not expressed in any culture.


CONCLUSIONS
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.
Jäger
M
M
Department of Orthopaedics, Heinrich-Heine University Hospital Duesseldorf, D-40225 Duesseldorf, Germany. Jaeger@med.uni-duesseldorf.de
Schultheis
A
A
Westhoff
B
B
Krauspe
R
R
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002356:Cartilage / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002804:Chondroblastoma / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology*; D010521:Periosteum / Q000166:cytology / Q000187:drug effects
D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate