Cellular Therapies for Type 1 Diabetes

Abstract

Type 1 diabetes mellitus (T1DM) is a disease that results from the selective autoimmune destruction of insulin-producing β-cells. This disease process lends itself to cellular therapy because of the single cell nature of insulin production. Murine models have provided opportunities for the study of cellular therapies for the treatment of diabetes, including the investigation of islet transplantation, and also the possibility of stem cell therapies and islet regeneration. Studies in islet transplantation have included both allo-and xeno-transplantation and have allowed for the study of new approaches for the reversal of autoimmunity and achieving immune tolerance. Stem cells from hematopoietic sources such as bone marrow and fetal cord blood, as well as from the pancreas, intestine, liver and spleen promises either new sources of islets or may function as stimulators of islet regeneration. This review will summarize the various cellular interventions investigated as potential treatments of T1DM.

Promoting ectopic pancreatic fates: pancreas development and future diabetes therapies

“…Bone marrow derived stem cells have been examined most frequently, and can be used to either directly generate islet cells or to initiate endogenous regeneration of the pancreas (81-86). Other adult stem cell populations that may be used include umbilical cord, intestinal, liver, adipose and spleen (87-90). Although their existence remains controversial, pancreatic stem cells may also provide a rich source of cells (87, 91, 92).…”

Hydrodynamics-Based Transfection of the Combination of Betacellulin and Neurogenic Differentiation 1 DNA Ameliorates Hyperglycemia in Mice with Streptozotocin-Induced Diabetes

“…1 This disease process lends itself to cellular therapy because of the single-cell nature of insulin production. 2 Although pancreatic islet transplantation for type 1 diabetes mellitus offers improved glycemic control through restoration of insulin production and freedom from life-threatening hypoglycemic episodes, 3 it is limited by the scarcity of donors and the requirement of chronic immunosuppressive therapy regimens. 4 The liver is a major target of insulin action, plays a critical role in maintaining glucose homeostasis, and contains many multipotent progenitor cells, 5,6 therefore making it a suitable target organ for gene therapy in the case of type 1 diabetes mellitus.…”

Subcutaneous transplantation of embryonic pancreas for correction of type 1 diabetes

“…This superficial site offers many advantages such as no-risk transplant placement, noninvasive imaging, and ability to perform repeated transplants if necessary. In addition, the use of embryonic tissue eliminates the need for large numbers of donor islets and can be customized for human patients by using stem cell-derived islet-like cell clusters (27,30,33,52,56). In the current experiments with immune-deficient nude mice and NOD-SC mice, embryonic pancreata survived in the subcutaneous space with no additional facilitation techniques and produced remarkable improvement of glucose homeostasis and body weight.…”