Role of Substrates in Diabetes Therapy:Stem Cell Differentiation and Islet Transplantation

Abstract

Type 1 diabetes affects more than a million people in the United States and many more across the world. While pharmaceutical interventions and insulin supplementation are the most commonplace treatment of diabetes, these are not essentially cures and can potentially lead to long-term complications. Transplantation of insulin-producing Islets of Langerhans from donor pancreas has been established as a promising alternative to diabetes therapy. While successful islet transplantation has the potential of providing a cure, the primary hurdles to be overcome for it to be clinically viable are the scarcity of donor islets and immune rejection of transplanted islets. Recent advances in stem cell culture and differentiation techniques have established stem cells as a likely source of transplantable islets. Different stem cell sources have been induced toward pancreatic differentiation using specific chemical perturbations along with use of specific substrates. An approach to overcoming the second hurdle of immune rejection of transplantable islets is to encapsulate the islets in specific biomaterials. In this review, we discuss the extensive use of various substrates for pancreatic differentiation of different stem cell sources, along with different biomaterial designs used for islet transplantation.

Administration of human umbilical cord blood mononuclear cells restores bladder dysfunction in streptozotocin‐induced diabetic rats

“…In diabetes‐induced tissue damage, stem cells give rise to specialized new functional cells by multilineage differentiation and self‐renewal, as well as inducing paracrine effects through the release of bioactive components in the wound area . Thus, stem cells could improve bladder function as a result of the migration and differentiation of cells, as well as paracrine effects .…”

“…Thus, stem cells could improve bladder function as a result of the migration and differentiation of cells, as well as paracrine effects . Stem cells can exert paracrine and immunomodulatory effects by decreasing diabetes‐induced inflammation and hypoxia …”

“…[1][2][3] The connection between diabetes and urinary bladder is largely unknown, and several pharmacological and surgical interventions have been shown to be ineffective therapy for diabetic bladder dysfunction. 4 In diabetes-induced tissue damage, stem cells give rise to specialized new functional cells by multilineage differentiation and selfrenewal, 5,6 as well as inducing paracrine effects through the release of bioactive components in the wound area. 7,8 Thus, stem cells could improve bladder function as a result of the migration and differentiation of cells, as well as paracrine effects.…”

Effects of β-like cell autotransplantation through hepatic arterial intervention on diabetic dogs

“…Injection of exogenous insulin, which cannot simulate the secretion of the endogenous one, easily leads to fl uctuation of blood sugar level and even hypoglycemia (Jun 2010;van Dieren et al 2010). Although patients with severe islet cell damages can be subjected to pancreas transplantation, the donors are limited and there may be immunological rejection (Candiello et al 2011). Th erefore, new therapies for diabetes are still needed.…”

Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model

“…Porcine islet xenotransplantation is being studied as an alternative to human islet allotransplantation since this option would mitigate donor scarcity issues [16,17] by providing a virtually limitless source of islets [18]. Also, porcine insulin being structurally similar to human insulin [19], has been used to treat T1D patients for decades [20].…”