Stemcell Research & Evidence - Diabetes
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Mesenchymal stem cell-based therapy for the treatment of type 1 diabetes mellitus
Curr Stem Cell Res Ther. 2012 May;7(3):179-90.
Dr. Soliman Fakeeh Hospital, Hematology Unit, Jeddah, Kingdome of Saudi Arabia.
The pathophysiology of Type 1 diabetes (T1D) appears largely related to an innate defect in the immune system culminating in a loss of self tolerance and destruction of the insulin producing β-cells. Currently, there is no definitive cure for diabetes. Insulin injection does not mimic the precise regulation of β-cells on glucose homeostasis, leading long term to the development of complications. Other therapeutic approaches therefore, are necessary and cell therapy is thought to be a possible approach. In this sense, mesenchymal stem cells (MSCs) can offer a promising possibility that deserves to be explored. MSCs are multipotent non-hematopoietic progenitor cells. Their therapeutic potentials have recently been brought into the spotlights of many fields of research. Although the regenerative capabilities of MSCs have been a driving force to initiate studies testing their therapeutic effectiveness, their immunomodulatory properties have been equally exciting. MSCs possess specific immunomodulatory properties that would appear capable of disabling immune dysregulation that leads to β-cell destruction in T1D. Furthermore, MSCs can be sequentially cultured in specially defined conditions and their differentiation extends toward the β-cell phenotype and the formation of insulin producing cells (IPCs). To date, the role of MSCs in T1D remains completely unexplored. We herein summarize multiple strategies that have been proposed and tested for its potential therapeutic benefit for T1D.
Stem cell therapy to cure type 1 diabetes: from hype to hope
Stem Cells Transl Med. 2013 May;2(5):328-36.
Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA.
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.
The therapeutic role of endothelial progenitor cells in Type 1 diabetes mellitus
Regen Med. 2011 Sep;6(5):599-605.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Pancreatic β-cells sense and adjust the blood glucose level by secretion of insulin. In Type 1 diabetes mellitus, these insulin-producing cells are destroyed, leaving the patients incapable of regulating blood glucose homeostasis. At the time of diagnosis, most patients still have 20-30% of their original β-cell mass remaining. These residual β-cells are targets for intervention therapies aimed at preventing further autoimmune destruction, in addition to increasing the number of existing β-cells. Such a therapeutic option is highly desirable since it may lead to a full recovery of newly diagnosed patients, with no need for further treatment with immunosuppressant drugs or exogenous insulin administration. In this article, we propose that endothelial progenitor cells, a cell type known to promote and support neovascularization following endothelial injury, may be used as part of a combinational stem cell therapy aimed to improve the vascularization, survival and proliferation of β-cells.
Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes
Diabetes Metab. 2009 Apr;35(2):85-93.
Inserm U697, Paris, France.
Mesenchymal stem cells (MSCs) are multipotent non-haematopoietic progenitor cells that are being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential together with their effects on immune response make them a promising therapeutic tool for severe refractory autoimmune diseases. Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic beta cells. While insulin replacement represents the current therapy for type 1 diabetes, its metabolic control remains difficult, as exogenous insulin cannot exactly mimic the physiology of insulin secretion. Pancreatic or islet transplantation can provide exogenous insulin independence, but is limited by its intrinsic complications and the scarcity of organ donors. In this context, stem cell therapy, based on the generation of insulin-producing cells (IPCs) derived from MSCs, represents an attractive possibility. In this review, we provide a brief characterization of MSC immunomodulatory effects, and present the current experimental evidence for the potential therapeutic efficacy of MSC transplantation in diabetes.
Mesenchymal stem cell therapy for diabetes through paracrine mechanisms
Med Hypotheses. 2008 Sep;71(3):390-3.