Director: Mark A. Atkinson, Ph.D.


Identifying the therapeutic potential of umbilical cord blood (UCB) for tolerance induction, and defining the role for two UCB constituents (i.e., Treg, mesenchyml stem cells (MSC)) in the process of imparting immune regulation.


We recently received FDA approval for a highly innovative pilot study aimed at the reversal of recent onset T1D utilizing autologus UCB transfusion in that study’s protocol, initially approved for 14 individuals, subjects with recent onset T1D receive intravenous infusion of autologus UCB (obtained from banked material). The primary purpose of this effort is designed to address issues related to safety, whereas questions related to the metabolic and immunologic aspects are subject to farm more limited investigation. That trial (which is ongoing but nearing enrollment completion at the time of this application’s submission) has, in fact, proven a success in that the therapy not only appears “safe” but in addition, a trend suggestive of a potential therapeutic benefit has been identified. At the same time, a clear need for improving and expanding this line of investigation exists in that our knowledge of the mechanisms underlying this form of intervention remains poor. Furthermore, recent advances in our understanding of immune regulation provided by Treg and MSC suggest additional, perhaps even improved opportunities for therapeutic intervention utilizing these cells, when derived from UCB, are warranted. Taking these notions together, we believe the studies proposed in this Center/Academic R&D application represent a novel opportunity to identify the therapeutic capacity of UCB and its cellular constituents to prevent/reverse T1D, induce tolerance, and understand the contributions of Treg and MSC to both the process of tolerance induction as well as the pathogenic defects which underly the natural history of T1D.

Description of Project

The overall purpose of this Center application is to test whether T1D can be prevented or reversed by transfusion of UCB or two populations of cells derived from UCB, Treg and MSC. In addition to evaluating therapeutic efficacy, the Center’s Projects and Cores seeks to collectively improve our mechanistic understanding of the potential of UCB to modulate immune reactivities (in general) and induce tolerance in an autoimmune setting, with particular focus on the role for Treg and MSC in these processes. The successful completion of these studies could uncover an innovative method for curing T1D as well as for inducing tolerance, establish the foundation for additional/expanded investigations on the potential for this therapy to treat immune based-disorders, and expand our insights as to the role for Treg and MSC in the process of immune regulation in early childhood.

Anticipated Outcomes

The successful completion of these studies will impact an extensive number of significant needs, includeing: 1) To uncover novel means for safe-yet-effective cell based therapies for tolerance induction and in this particula case, T1D prevention and reversal; 2) To understand the immunoregulatory potential of UCB, as well as the role for Treg and MSC in this process; 3) To identify novel assays of cellular immunity and immune tolerance in T1D; 4) To understand key differences in the regulatory capacity of UCB versus other tissue sources (i.e., peripheral blood, bone marrow) in early childhood.

Relevance to Type 1 Diabetes

The programs investigators believe that the information gleaned from these studies represent KEY underpinnings to uncovering a means to prevent or reverse type 1 diabetes.

Project 1: Autologus Umbilical Cord Therapies for Type 1 Diabetes, PI: Desmond A. Schatz

Project 2: Expanded Umbilical Cord Blood Regulatory T Cells for the Treatment of T1D, PI: James L. Riley

Project 3: Immunomodulatory Functions of Human MSCs in Type 1 Diabetes, PI: Mohamed H. Sayegh

Core A: Administrative Core, PI: Mark A. Atkinson

Core C: The Humanized Mouse Core, PI: Dale L. Greiner

Core D: Cell Separation and Expansion Core, PI: Bruce L. Levine