Regeneration of Pancreatic Beta-Cell Mass Using Embryonic and Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes Mellitus
Alesha White
Introduction. Type 1 diabetes mellitus (T1DM) is an autoimmune condition that depletes b cell mass and insulin production thus rendering patients incapable of regulating glucose levels1-4. Patients often present with symptoms between the ages of 5 and 7 and over time, T1DM is noted for causing multi-organ failure2-3. In 2016, T1DM was noted as having an increasing incidence rate of 30-50/100,000 persons2. Current treatments for T1DM include insulin injections, pancreatic islet transplantation and whole pancreas transplantation2-4. Although these methods of treatment have been successful for many patients, scientists have begun to look for ways to restore b cell volume and protect against autoimmune attack using embryonic (ESCs) and mesenchymal stem cells (MSCs) respectively. Methods. Many studies focus on the use of ESCs as a means of replacement of non-functional b cells5-6. In vitro ESCs are induced to pancreatic progenitor stem cells and then are introduced in vivo to diabetic mice to mature to fully functioning b cells. Many studies site different growth cultures that aid in the differentiation of cells into functional progenitor stem cells in a quantity that is sufficient to improve glucose tolerance. Another focus of stem cell treatment is placed on the use of MSCs as a means of autoimmune protection7-8. Many studies site that the autoimmune attack in T1DM is mediated largely by CD4+ T helper 1 (TH1) cells7-8. MSCs have been shown to suppress the immune response by inhibiting the activity of T cells and by increasing the production of regulatory T cells (Tregs)8. Studies using MSCs inject MSCs into diabetic mice and monitor levels of TH1 cells, Tregs and certain factors produced by MSCs that may protect cells against autoimmune attack. Results. In experiments using ESCs, transplantation of stem cells has the ability to deliver differentiated b progenitor cells to diabetic mice and induce to some extent insulin expression5-6. In experiments using MSCs, levels of TH1 cells are often decreased while levels of Tregs are increased8. Certain factors produced by MSCs also, such as TIMP-1, are shown to have a protective effect on b cell mass when challenged with pro-inflammatory cytokines7. Conclusions. Overall treatment with both forms of stem cells decreases symptoms of hyperglycemia by restoring b cell mass and in mice may be an effective means of treatment for T1DM. Despite these positive findings, there are some shortcomings of stem cell transplantation that suggest more research is needed before stem cells can be used in humans as an established treatment for T1DM.
- Bose B, Shenoy SP, Konda S, Wangikar P. Human embryonic stem cell differentiation into insulin secreting β-cells for diabetes. Cell Biology International. 2012; 36:1013–1020.
- Vanikar AV, Trivedi HL, Thakkar UG. Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus Cytotherapy. 2016;18(9):1077-1086.
- Lilly MA, Davis MF, Fabie JE, Terhune EB, Gallicano GI. Current stem cell based therapies in diabetes. American Journal of Stem Cells. 2016; 5(3):87-98.
- Bouwens L, Houbracken I, Mfopou JK. The use of stem cells for pancreatic regeneration in diabetes mellitus. Nature Reviews Endocrinology. 2013; 9(10):598-606.
- Pagliuca F, et al. Generation of functional human pancreatic b cells in vitro. Cell. 2014;159(2):428-439.
- Sneddon J, Borowiak M, Melton D. Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme. Nature. 2012;491:765-770.
- Kono T, Sims E, Moss D, et al. Human adipose-derived stromal/stem cells protect against STZ-induced hyperglycemia: analysis of hASC-derived paracrine effectors. Stem Cells. 2014;32:1831-1842.
- Bassi E, Moraes-Vieira M, Moreira-Sa C, et al. Immune regulatory properties of allogenic adipose-derived mesenchymal stem cells in the treatment of experimental autoimmune diabetes. Diabetes. 2012;61(10):2534-2545.