Science et thérapie du cancer

Silicate Granules Preconditioned with Human Bone Marrow Mononuclear Cells Improve Osteogenesis in Bone Sarcoma Patients

Abstract

Filomena de Nigris, Flavio Fazioli, Gianluca Colella, Rosa Camerlingo, Roberta Miceli, Mariano Giuseppe Di Salvatore and Giuseppe Pirozzi

Background: Poor bone regeneration is a devastating complication after large tumor resection. Different synthetic bone-grafting materials have been used to restore skeletal defects. Several studies evaluated the capability of mesenchymal stem cells to improve the efficacy of bone regenerative potential of biomaterials. However, there are no data, in human, about the combinatory use of silicate granules with autologous Bone Marrow Mononuclear cells (BMMCs) to refill bone cavity.

Methods: BMMCs were prepared in accordance with the International Society for Cell Therapy guidelines. MTT assays and scanning electron microscopy evaluated the biocompatibility, and adhesion of BMMCs to the granular silicate bone substitute. In vivo study is based on twenty patients with malignant osteolytic lesions. The mean volume of the lesions, measured by pre-operative computed tomography (CT) was 18.5 cm2 (range 16-24 cm2). Sixteen patients were treated post-surgery with curettage and refilling with granular silicate alone, and four with a combination of granular silicate and BMMCs The follow-up was determined by clinical, Musculoskeletal Tumor Society functional state score system (MSTS), and radiograph examination, moreover, the callus type was classified according to the International System.

Results: Scanning electron microscopy showed that 90% of BMMCs adhered to silicate granules in a few minutes and long pseudopodia contacting extra-cellular matrix. Patients treated with autologous BMMCs and granular silicate developed bone callus after two weeks. The follow-up of limbs functional state measured by MSTS was a mean of 82% compared to mean of 60% obtained with granules alone. At the end of the follow-up (minimum one year), all the patients were cancer-free with an excellent outcome.

Conclusions: The encouraging results of our early study indicate that refilling at the osteotomy site with autologous BMMCs and granular silicate improves bone repair. A larger study cohort and longer follow-up times are required to identify additional predictors and indications.