A therapy that includes stem cell transplantation induced extended insulin independence in patients with type 1 diabetes mellitus, according to a preliminary study in the April 11 issue of JAMA.

Type 1 diabetes mellitus (DM) results from a cell-mediated autoimmune attack against pancreatic beta cells. At the time of clinical diagnosis, approximately 60 percent to 80 percent of the beta-cell mass has been destroyed, according to background information in the article. Beta-cell preservation has been shown to be an important target in the management of type 1 DM and in the prevention of its related complications.

Julio C. Voltarelli, M.D., Ph.D., of the University of São Paulo, Ribeirão Preto, Brazil, in collaboration with Richard Burt, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues conducted a study to examine the effect of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) to preserve beta-cell function in 15 newly diagnosed patients with type 1 DM. AHST, which uses a patient’s own blood stem cells, involves the removal and treatment of the stem cells, and their return to the patient by intravenous injection.

During a 7 to 36-month follow-up, 14 patients became insulin-free (one for 35 months, four for at least 21 months, seven for at least six months; and two with late response were insulin-free for one and five months, respectively). Among those, one patient resumed insulin use one year after AHST. The only severe adverse effects were pneumonia in one patient and endocrine dysfunction in two others.

“This is, to our knowledge, the first report of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation for human type 1 DM. Very encouraging results were obtained in a small number of patients with early-onset disease. Ninety-three percent of patients achieved different periods of insulin independence and treatment-related toxicity was low, with no mortality. Further follow-up is necessary to confirm the duration of insulin independence and the mechanisms of action of the procedure. In addition, randomized controlled trials and further biological studies are necessary to confirm the role of this treatment in changing the natural history of type 1 DM and to evaluate the contribution of hematopoietic stem cells to this change,” the authors conclude.

(JAMA. 2007;297:1568-1576. Available pre-embargo to the media at http://www.jamamedia.org)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Cellular Therapy for Type 1 Diabetes - Has the Time Come?

In an accompanying editorial, Jay S. Skyler, M.D., of the Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, comments on the study on type 1 diabetes and stem cell transplantation.

“This study by Voltarelli et al is the first of what likely will be many attempts at cellular therapy to interdict the type 1 DM disease process. Other approaches under consideration include infusion of dendritic cells, T-regulatory lymphocytes, umbilical cord cells, embryonic or adult stem cells, and allogenic bone marrow transplantation in addition to further studies with autologous hematopoietic stem cell transplantation. Research in this field is likely to explode in the next few years and should include randomized controlled trials as well as mechanistic studies. As these further studies confirm and build on the results of Voltarelli et al-the time may indeed be coming for starting to reverse and prevent type 1 DM.”

Source: American Medical Association (AMA)