Stem cell therapy to cure type 1 diabetes: from hype to hope

Abstract

Type 1 diabetes mellitus (T1D) is a chronic, multifactorial autoimmune disease that involves the progressive destruction of pancreatic β-cells, ultimately resulting in the loss of insulin production and secretion. The goal of clinical intervention is to prevent or arrest the onset and progression of autoimmunity, reverse β-cell destruction, and restore glycometabolic and immune homeostasis. Despite promising outcomes observed with islet transplantation and advancements in immunomodulatory therapies, the need for an effective cell replacement strategy for curing T1D still persists. Stem cell therapy offers a solution to the cited challenges of islet transplantation. While the regenerative potential of stem cells can be harnessed to make available a self-replenishing supply of glucose-responsive insulin-producing cells, their immunomodulatory properties may potentially be used to prevent, arrest, or reverse autoimmunity, ameliorate innate/alloimmune graft rejection, and prevent recurrence of the disease. Herein, we discuss the therapeutic potential of stem cells derived from a variety of sources for the cure of T1D, for example, embryonic stem cells, induced pluripotent stem cells, bone marrow-derived hematopoietic stem cells, and multipotent mesenchymal stromal cells derived from bone marrow, umbilical cord blood, and adipose tissue. The benefits of combinatorial approaches designed to ensure the successful clinical translation of stem cell therapeutic strategies, such as approaches combining effective stem cell strategies with islet transplantation, immunomodulatory drug regimens, and/or novel bioengineering techniques, are also discussed. To conclude, the application of stem cell therapy in the cure for T1D appears extremely promising.

Figure 1.

Stem cell strategies for the cure of T1D. Stem cell-based strategies to restore glycometabolic and immune homeostasis are based on the intrinsic regenerative capacity as well as the immunomodulatory potential of stem cells. The regenerative capacity can be harnessed to make available a self-replenishing supply of glucose-responsive insulin-producing cells for transplantation. The immunomodulatory properties can potentially be harnessed to arrest β-cell destruction, preserve residual β-cell mass, facilitate endogenous β-cell regeneration, ameliorate innate/alloimmune graft rejection, and prevent the recurrence of autoimmunity. Abbreviations: BM-HSC, bone marrow-derived hematopoietic stem cell; iPSC, induced pluripotent stem cell; MSC, mesenchymal stromal cell; T1D, type 1 diabetes mellitus; Treg, regulatory T cell.

Figure 2.

Combinatorial strategies for treatment of T1D. Combining safe and effective stem cell strategies with reliable existing therapies such as islet transplantation, as well as the latest immunosuppressive and immunomodulatory drug regimens and/or novel bioengineering techniques and/or gene therapies, would ensure an optimistic scenario for successful translation of stem cell therapy in the cure of T1D. Abbreviations: Ag, antigen; DPPIV, dipeptidyl peptidase IV; IgM, immunoglobulin M; T1D, type 1 diabetes mellitus; Treg, regulatory T cell.