CCUMULATED CLINICAL EXPErience indicates that there is an inverse association between beta-cell function and chronic complications of type 1 diabetes mellitus (DM)-the higher the Cpeptide levels (an indirect measure of viable beta-cell function), the lower the incidence of microvascular complications of type 1 DM. 1 Since the establishment of the autoimmune etiology of type 1 DM in the late 1970s, many clinical trials analyzing the effects of different types of immune interventions demonstrated that beta-cell preservation is an achievable target in different degrees. 2,3 Based on the theory of possible reconstitution of immune tolerance after "immunologic reset" with autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT), 4 in 2007, we reported a phase 1/2 trial evaluating the safety and metabolic effects of autologous nonmyeloablative HSCT in 15 patients with newly diagnosed type 1 DM. 5 The majority of pa-Author Affiliations are listed at the end of this article.

Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/ rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intratransplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P ¼ 0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for a ll patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P ¼ 0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term followup would be required to fully assess the differences in therapeutic effectiveness between the two regimens.

In this review, we present (1) the scientific basis for the use of high-dose immunosuppression followed by autologous peripheral blood hematopoietic stem cell transplantation for newly diagnosed type 1 diabetes (T1D); (2) an update of the clinical and laboratory outcome of 20 patients transplanted at the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, and followed up to January/2008, including 4 relapses among 19 patients without previous ketoacidosis; (3) a commentary on criticisms to our article that appeared in four articles from the scientific literature; and (4) a discussion of the prospectives for cellular therapy for T1D.

Nesta revisão são discutidas várias alternativas de regeneração do conjunto de células produtoras de insulina do pâncreas, usando células-tronco embrionárias do cordão umbilical e adultas, e o trabalho que está sendo realizado em nosso grupo de pesquisas utilizando imunossupressão em altas doses combinada com a infusão de células-tronco hematopoéticas autólogas em diabete do tipo 1 recém-diagnosticado. Rev. Bras.