[Treatment of bone diseases with cell therapy].

V Gangji
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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.

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[用细胞疗法治疗骨病]。
股骨头坏死是一种影响年轻患者的罕见疾病,其特征是股骨头发生坏死病变,死骨失去机械阻力和股骨头塌陷。患者抱怨髋关节疼痛和功能丧失,这可能导致全髋关节置换术。到目前为止,骨坏死被认为是一种血管疾病,由于血管断裂或压迫导致骨坏死。我们认为骨坏死是一种骨病,对其进行了生理病理研究。我们和其他团队证明,骨坏死患者的间充质干细胞(骨细胞和成骨细胞的前体)数量减少。我们启动了一项对照双盲试验,研究从浓缩骨髓中获得的干细胞植入骨坏死区的疗效。本研究显示骨髓移植可以延缓疾病进展至骨折期,改善髋关节疼痛和关节症状。然后,我们试图通过开发成骨细胞形成的骨细胞治疗产品来改善这种治疗方法。研制了一种由成骨细胞形成的新型细胞治疗产品PREOB。PREOB在股骨头坏死的随机对照II期试验中进行了测试,与浓缩骨髓相比,PREOB具有优势。如今,这种细胞治疗产品是由“布鲁塞尔自由大学”的衍生公司Bone Therapeutics开发的。其他骨病的特点是干细胞活性降低,例如由于骨不愈合骨折而无法满足骨重塑的需要。临床研究也表明浓缩的骨髓可以移植到骨不愈合处。然而,其效果依赖于移植干细胞的数量。细胞治疗产品目前正在I期试验中进行测试,初步结果很有希望。骨疾病的细胞治疗是一种新的治疗方法,从干细胞发展到使用感兴趣的分化细胞。
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