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Stem Cell Therapy: Recent Success and Continuing Progress in Treating Diabetes Elton Mathias1*, Roveena Goveas2 and Manish Rajak1

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Stem Cell Therapy: Recent Success and Continuing Progress in Treating Diabetes Elton Mathias1*, Roveena Goveas2 and Manish Rajak1 ISSN: 2469-570X Mathias et al. Int J Stem Cell Res Ther 2018, 5:053 DOI: 10.23937/2469-570X/1410053 Volume 5 | Issue 1 International Journal of Open Access Stem Cell Research & Therapy REVIEW ARTICLE Stem Cell Therapy: Recent Success and Continuing Progress in Treating Diabetes Elton Mathias1*, Roveena Goveas2 and Manish Rajak1 1 Check for Innvocept Solutions, Mumbai, India updates 2Department of Internal Medicine, Mountainside Medical Center, Montclair, USA *Corresponding author: Elton Mathias, Medical Professional, Innvocept Solutions, Mumbai, India, Tel: +1-(732)-804- 5257, E-mail: [email protected] at any age, but most often occurs in children and young Abstract adults. The etiology of DM type 1 is not fully uncovered, Diabetes mellitus (DM), a cluster of metabolic diseases, re- however in most cases, the body’s immune system at- sulting in high blood glucose levels, is prevalent in today’s world. The global costs of diabetes and its consequences tacks and destroys insulin producing beta-cells. Family are rising and are expected substantially increase by 2030, history is known to play a role, in about 10% to 15% of especially in middle- and lower-income countries. Evi- people with DM type 1. Type 2 diabetes, also known as dence-based therapies, specifically targeting the reduction adult-onset DM, which usually develops after the age of high blood glucose levels, and minimizing diabetic com- of 40 but can appear earlier in obese patients. With plications, are currently the choice of treatment. Stem cell therapy offers a promising vision to treat DM. Although chal- DM type 2, the pancreas produces insulin, but the body lenges are still posed with this line of therapy, studies have cannot use it effectively. Insulin treatment is not always produced regenerative beta-cells which closely resemble necessary, in these patients, as with DM type 1. Diabe- insulin-secreting cells. A number of sources for stem cells tes mellitus is associated with severe long-term micro- have been explored, ever since the proof-of-concept for cell therapy was laid down. This review summarizes stem cell and macrovascular complications and carries a high therapy in the treatment of DM. rate of morbidity and mortality. Both DM type 1 and 2 are a significant public health concern with numerous Keywords debilitating complications. The global costs of diabe- Stem cells, Diabetes, Islets, Pancreas tes and its consequences are rising and are expected substantially increase by 2030 [1], especially in middle- Introduction and lower-income countries. Evidence-based therapies, According to the WHO report released in November specifically targeting the reduction of high blood glu- 2017 the number of people with Diabetes mellitus (DM) cose levels, and minimizing diabetic complications, are has risen from 108 million in 1980 to 422 million in 2014 currently the choice of treatment [3]. [1]. The prevalence of DM across all age-groups, world- The pathogenesis of DM, whether type 1 or type 2, wide was estimated to be 2.8% in 2000 and is expected can be traced back to the dysfunction of the pancreatic to rise to 4.4% by 2030, with the total number of people beta-cells. Although approved therapies that enhance with DM projected to rise from 171 million in 2000, to beta-cell function exist, there are none that lead to 636 million in 2030 [2]. the regeneration of the lost or dysfunctional beta-cell There are two types of DM - type 1 and type 2. Type [4]. Studies have shown that beta-cells can be repro- 1 diabetes, also known as insulin-dependent diabetes grammed, with certain molecules, such as GABA [5] and juvenile diabetes, involves the immune system, and hormone [6]. However, these studies also bring to which results from a cellular-mediated autoimmune de- light a lot of uncertainties that need to be explored [4]. struction of the BETA-cells of the pancreas. It can occur Stem cells for the treatment of DM come from a variety Citation: Mathias E, Goveas R, Rajak M (2018) Stem Cell Therapy: Recent Success and Continuing Progress in Treating Diabetes. Int J Stem Cell Res Ther 5:053. doi.org/10.23937/2469-570X/1410053 Accepted: June 26, 2018: Published: June 28, 2018 Copyright: © 2018 Mathias E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Mathias et al. Int J Stem Cell Res Ther 2018, 5:053 • Page 1 of 8 • DOI: 10.23937/2469-570X/1410053 ISSN: 2469-570X Figure 1: Formation of differentiated cells and specialized cells from stem cells and progenitor cells. of biological sources like embryos, placenta, and bone Islet transplants are a safer option than whole pancreas marrow. Progenitor cells are another exciting avenue transplants. The procedure to insert donor islet cells is of research. Like stem cells, these cells can take on the far less critical than transplanting a complete pancreas. form of a number of different types of mature human For any type of transplantation procedure, a balance is cells, however, unlike stem cells, they cannot divide in- sought between efficacy and toxicity. With respect to definitely. islet transplantation a main concern was that many of Progenitor stem cells have been used to grow insulin the current agents’ cause damage beta cells or induce producing cells, under laboratory conditions, from in- peripheral insulin resistance [8,9]. Immunosuppressant drugs also can cause problems, as suppressing the im- testinal cells and undeveloped pancreatic cells [7]. This article provides an overview of the various approaches mune system raises the risk of infection [10]. used to regenerate pancreas in patients with diabetes, Shapiro, et al., reported insulin independence, with recent advances including our contributions and also a tight glycemic control and correction of glycated he- novel approach that may be explored in future. moglobin levels, in seven consecutive subjects treated Progenitor cell are very similar to stem cells. They with glucocorticoid-free immunosuppressive therapy are biological cells and like stem cells, they too have the combined with infusion of an adequate mass of freshly ability to differentiate into a specific type of cell. How- prepared islets from two or more pancreases from de- ever, they are already more specific than stem cells and ceased donors [11]. This treatment came to be known can only be pushed to differentiate into its “target” cell. as the Edmonton Protocol [12]. In continuation to this Whereas, stem cells have the ability to differentiate into protocol, a phase I/II clinical trial was undertaken to many different types of cells as shown inFigure 1. Com- demonstrate the feasibility and reproducibility of the parison between Stem Cell and Progenitor Cell are high- outcomes of the Edmonton protocol. The trial conclud- lighted in detail in Table 1. ed that though long-term endogenous insulin produc- tion and glycemic stability in subjects with type 1 dia- Islet Cell Transplants betes mellitus was achieved, it was found that insulin Pancreatic islets include the insulin producing beta independence was more than often not sustainable, cells, which are crucial in regulating blood glucose levels. and gradually lost in the long run [13]. Mathias et al. Int J Stem Cell Res Ther 2018, 5:053 • Page 2 of 8 • DOI: 10.23937/2469-570X/1410053 ISSN: 2469-570X Table 1: Comparison between Stem Cell and Progenitor Cell. Comparison in Stem Cell Progenitor Cell Description Stem Cells are reserve cells that have the ability to change Progenitor cell are very similar to stem cells. They into many different types of cells and grow indefinitely. They are biological cells and like stem cells, they too have have the potential to create many new different cells that can the ability to differentiate into a specific type of cell. help replace dying and/or damaged cells. Stem cells also However, they are already more specific than stem have the potential to create new tissue and even whole or- cells and can only be pushed to differentiate into its gans from just a few stem cells. "target" cell. Types Four main types of stem cells: Many, as each "target" cell has its own progenitor 1. Adult or somatic stem cells cell. Some of the types include: 2. Fetal stem cells 1. Satellite cells found in muscles. 3. Embryonic stem cells 2. Intermediate progenitor cells formed in the subventricular zone. 4. Induced stem cells 3. Bone marrow stromal cells 4. Periosteum contains progenitor cells that de- velop into osteoblasts and chondroblasts. 5. Pancreatic progenitor cells 6. Angioblasts or endothelial progenitor cells (EPC) 7. Blast cells Features 1. Multiply by cell division to replenish dying cells and regen- 1. Tendency to differentiate into a specific type erate damaged tissues. of cell, but is already more specific than a 2. Generate all the cell types of the organ from which they stem cell and is pushed to differentiate into its originate. "target" cell. 3. Potentially regenerating the entire organ from a few cells. 2. Can divide only a limited number of times. Benefits They have the potential to increase healing and for potentially They act as a repair system for the body. They re- regenerating an entire organ from a few cells. They are inves- plenish special cells, but also maintain the blood, tigated in treatment of: skin and intestinal tissues. Progenitor cells can 1. Diabetes be activated in case of tissue injury, damaged or dead cells. It leads to the recovery of the tissue. 2. Rheumatoid arthritis 3. Parkinson's disease 4. Alzheimer's disease 5. Osteoarthritis 6. Stroke and traumatic brain injury repair 7.
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