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Clinical research

Autologous hematopoietic stem cell transplantation for therapy of autoimmune and inflammatory diseases

The clinical trials focusing in the use of high-dose immunosuppression associated to autologous hematopoietic stem cell transplantation (HSCT) for therapy of autoimmune and inflamatory diseases will continue and evolve to new developments. Treatment of multiple sclerosis with HSCT in phase I/II trials was performed in 30 patients and the course of the disease stabilized or improved in most patients. Thus, we plan to engage in a phase III international trial comparing HSCT with the best available pharmacological treatment for MS (mitoxantrone).

Current phase I/II trial of HSCT for early-onset type I diabetes mellitus which shows very promising results will be completed and a new one for early-onset amyotrophic lateral sclerosis will be open. More experience should be gained in rheumatic diseases (systemic lupus, systemic sclerosis and others) before engaging in phase III trials.In addition, experimental models of autoimmune/inflammatory diseases (inflammatory bowel disease, idiopathic pulmonary fibrosis and others) will be developed and treated with various forms of HSCT. A further development of these studies will be the use of stem cells from different sources (hematopoietic, mesenchymal and embryonic) for tissue regeneration in cardiac, neurologic and degenerative diseases.

The use of mesenchymal stem cells as suppressor cells in haploidentical stem cell transplantation for advanced neoplastic diseases.

Stem cell transplantation is the only curative approach for several hematological and non hematological diseases. Unfortunately a large proportion of patients will not have a matched sibling for transplant. Thus, grafts from other sources, not only from unrelated donors but also cord blood has been used. Unsatisfactory results with mismatched donnors, especially because of graft versus host diseases and graft failure, could be reverted after the use of high doses of stem cell infusion introduced since 1990. The demonstration that megadose CD34 positive cells exert suppressor activity against activated T cells opened the way for the use of these cells in mismatched transplants.

More recently, mesenchymal stem cells have been shown to have similar imunossupressive effects in animal tumor models and in T cell proliferation and dendritic function in vitro. As mesenchymal stem cells also have been used for better engraftment, we supposed that the use of mesenchymal stem cells in a full-haplotype mismatched stem cell transplant could be able to improve engraftment while preventing GVHD. The use of full-haplotype mismatched mesenchymal stem cell infusion was already used in a case of severe GVHD with resolution of the disease.

Clinical Research