[Treatment of bone diseases with cell therapy]. / Le traitement des maladies osseuses par thérapie cellulaire.

ABSTRACT

Osteonecrosis of the femoral head is a rare disease that affects young patients and is characterized by the occurrence of a necrotic lesion in the femoral head, loss of mechanical resistance of dead bone and collapse of the femoral head. Patients complain of hip pain and loss of function that could lead to total hip replacement. So far, osteonecrosis was considered as a vascular disease due to vascular section or compression leading to bone necrosis. We studied the physiopathology of the osteonecrosis considering it as a bone disease. We demonstrated as well as other teams that the number of mesenchymal stem cells, precursors of bone cells and osteoblastic cells, were reduced in patients with osteonecrosis. We initiated a controlled double blind trial to study the efficacy of stem cells implantation--obtained from concentrated bone marrow--in the osteonecrosis zone. This study showed that bone marrow implantation could delay disease progression to the fractural stage and improve hip pain and joint symptoms. We then tried to improve this treatment by developing a bone cell therapy product formed of osteoblastic cells. A novel cell therapy product formed ofosteoblastic cells, PREOB was developed. PREOB was tested in a randomized, controlled phase II trial in osteonecrosis of the femoral head and showed its superiority compared to concentrated bone marrow. Today, this cellular therapy product is developed by Bone Therapeutics, a spin-offcompany of the "Université libre de Bruxelles". Other bone diseases are characterized by reduced activities of stem cells that are unable to meet the need of bone remodelling due to a non-union fracture, for example. Clinical studies also showed that concentrated bone marrow could be implanted into the non-union. However, its efficacy was dependent on the number of implanted stem cells. The cellular therapy product is currently tested in a phase I trial with promising preliminary results. Cellular therapy for bone diseases is a novel therapeutic approach that evolves from stem cells to the use of the differentiated cells of interest.