C-Peptide Levels and Insulin Independence Following Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus

Abstract

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.

Functional plasticity in human FOXP3+regulatory T cells

“…While this protocol proposes to induce Treg cells in vitro from Tconv cells, it offers several novel avenues. In particular, they suggest to create a lymphopenic environment, an idea supported by the successful, yet transient, improvement of this disease by HSCT following total conditioning, 35 and to use Treg-stabilizing treatment. 22 The potential results of such a clinical trial would certainly contribute a wealth of knowledge regarding the hopes of Treg-base immunotherapy, as it attempts to integrate a very large part of the current information, from both mice and men.…”

Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin

“…Recent studies, however, suggest that patients with type 1 diabetes may still have a large amount of remaining beta cells [4]; in some patients loss of BCM was less than 50% [5]. Moreover, some patients newly diagnosed with type 1 diabetes who underwent autologous nonmyeloablative haematopoietic stem cell transplantation became insulin-independent for several months, suggesting restored function of existing beta cells [6]. In type 2 diabetes, failure of beta cells to adapt to the increased insulin demand, posed by insulin resistance in target tissues, leads to impaired glucose homeostasis [1,[7][8][9][10].…”

Lineage tracing and resulting phenotype of haemopoietic-derived cells in the pancreas during beta cell regeneration

“…Transplantation of bone marrow cells, or separated fractions of marrow progenitor cells have been shown to facilitate the reversal of diabetes in experimental animals, and newly diagnosed individuals with type 1 diabetes [1][2][3][4]. In some studies a direct trans-differentiation of bone marrow stem cells into insulin-positive beta cells has been demonstrated, either in vivo or following lineage manipulation in vitro [5][6][7], but the direct contribution of haemopoietic stem cells to a new beta cell population has generally been found to be low and inconsistent with the associated increase in insulin secretion and normalisation of blood glucose [1,[8][9][10].…”