Cartilage restoration in haemophilia: advanced therapies

Abstract

Current treatment of joint cartilage lesions is based either on conventional techniques (bone marrow stimulation, osteochondral autograft or allograft transplantation) or on newly developed techniques (chondrocyte implantation and those based on cell therapy that use bioreactors, growth factors, mesenchymal stem cells [MSCs] and genetically modified cells). The aim of this article is to review the therapeutic strategies above mentioned and to determine whether the chondral damage seen in haemophilia could benefit from any of them. The different conventional techniques have shown similar results whereas autologous chondrocyte implantation, which is in common use at the present time, has not been shown to produce any conclusive results or to lead to the formation of hyaline cartilage. MSCs hold promise for the repair of joint cartilage given their differentiation capacity and the therapeutic effect. The use of bioreactors and growth factors, which stimulate cartilage formation, may optimize such strategies in the context of reimplantation of chondrocytes, differentiated MSCs and cartilage progenitor cells. The aim of cell therapy is restoration of function through the repair of damaged tissue or the stimulation of growth factor synthesis. Implantation of autologous chondrocytes or MSCs was up to now able to address only highly localized chondral lesions. Adequate control of the differentiation process as well as the use of growth factors and appropriate bioreactors could transform cell-based therapies into a more efficient and longer term treatment even for patients with haemophilia. Nevertheless, raising false expectations in these patients should be avoided. There are a number of approaches to cartilage restoration in haemophilic arthropathy, which are currently being explored for other joint related degenerative disorders. If it can be proven to be effective for the disorders in which clinical trials are ongoing and costs could be limited, it might be an useful palliative approach to haemophilic arthropathy. However, we still have a long way to go for use in haemophilic arthropathy.

Induced Pluripotent Stem Cells: Therapeutic Applications in Monogenic and Metabolic Diseases, and Regulatory and Bioethical Considerations

“…The current policy in developed countries is in general to administer a prophylactic treatment (2 or 3 times a week) from early childhood into adulthood [39]. Such prophylactic protocols result in a clear improvement in patients' quality of life on account of the prevention of haemophilic arthropaty and other fatal manifestations of the disease as well as a reduction in the long-term costs of treatment because of a decrease in the need of surgical procedures such as arthrodesis, arthroplasty or synovectomy [40].…”

“…The chief goal of these new strategies will be to address some of the shortcomings associated with current treatment options such as the short in vivo half-life of administered factors, the impending risk of a pathogen-induced infection and the development of inhibitors. Another goal of the advanced therapies (cell therapy) will be palliative treatment of the articular consequences derived from haemophilic arthropathy [40].…”

Advanced therapies for the treatment of hemophilia: future perspectives

“…Against this background, advanced therapies may constitute a solution of these patients [6]. Chondrocyte implantation and cell therapy using bioreactors, growth factors, mesenchymal stem cells and genetically modified cells may be used as an adjunct or even as an alternative to the current approaches (bone marrow stimulation, osteochondral autograft or allograft transplantation) for the repair of chondral damage in advanced arthropathic disease.…”

“…The current policy in developed countries is in general to administer a prophylactic treatment (2 or 3 times a week) from early childhood into adulthood [2]. Such prophylactic protocols result in a marked improvement in patients' quality of life on account of the prevention of hemophilic arthropathy and other fatal manifestations of the disease as well as a reduction in the long-term costs of treatment because of a decrease in the need of surgical procedures such as arthrodesis, arthroplasty or synovectomy [6]. …”

“…The chief goal of these new strategies will be to address some of the limitations associated with current treatment options such as the short in vivo half-life of administered factors, the risk of a pathogen-induced infection and the development of inhibitors. Another goal of the advanced therapies (cell therapy) will be palliative treatment of the articular consequences derived from hemophilic arthropathy [6]. …”