Académie royale de Médecine de Belgique

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Résumé de Valérie Gangji (Séance du 28.05.2011)

 

CELLULAR THERAPY TO TREAT BONE DISEASES

par  Mme V. GANGJI (Hôpital Erasme – U.L.B.), invitée.      

Bone marrow containing mesenchymal stem cells, precursors of osteoblastic cells could contribute to generation of mesenchymal tissues such as bone. In diseases, where a deficit has been shown in the number or function of mesenchymal stems cells or in osteoblastic cells, the tissue is unable to meet the needs of bone remodeling in the process of fracture or lesion healing. Therefore, bone marrow or concentrated bone marrow has been used in the treatment of osteonecrosis or nonunion.

Osteonecrosis of the femoral head is a painful disorder of the hip leading in its late stage to subchondral fracture and total hip replacement. Corticosteroids and alcohol abuse are among the most widely recognized risk factors in Caucasians. In early stages of the disease, core decompression of the femoral head was the most widespread procedure proposed to those patients with an efficacy that remains controversial. Accordingly, there have been calls for a pathophysiological approach to the treatment of osteonecrosis. In osteonecrosis, the levels of activity and the number of mesenchymal stem cells in both the haematopoietic and the stromal compartments of the bone marrow have been shown to be depressed. Moreover, we have previously shown that the capacity of proliferation of osteoblastic cells was decreased in the proximal femur of those patients. These findings raised the possibility that bone marrow containing stem cells for mesenchymal tissues including bone could be implanted into the necrotic lesion of the femoral head. Thereafter, we and another team studied the efficacy of bone marrow transplantation in osteonecrosis of the femoral head. We showed that bone marrow implantation into the necrotic lesion improved hip symptoms and delayed disease progression. However, new methods are needed to improve the efficacy and specificity of those existing cellular therapies by either optimizing the number of mesenchymal stem cells administered or producing the cells of interest.

In order to improve the cellular product, a pure osteoblastic cell population (PREOB®-Bone Therapeutics) derived from mesenchymal stem cells was developed. This population is characterized by its negativity for hematopoietic cell markers (CD14 and CD19) and its positivity for a mesenchymal stem cell marker (CD 105). The osteoblastic phenotype of the product was confirmed by its ability to synthesize biologically active alkaline phosphatase (ALP), to secrete and mineralize bone matrix and by high levels expression of bone growth factors and matrix proteins which are important readouts of osteogenic differentiation. This osteoblastic cell population is currently studied in the treatment of osteonecrosis of the femoral head and in nonunion fracture.

In conclusion, pioneer trials of bone marrow implantation in osteonecrosis and nonunion have demonstrated their safety and efficacy. However, larger controlled and randomized trials are needed to confirm those results. Improvement of clinical results can be possible through optimization of the cellular product by the improvement of intraoperative bone marrow harvest/concentration or the selection of subpopulations of cells.

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