The Feasibility and Applicability of Stem Cell Therapy for the Cure of Type 1 Diabetes.
Ontology highlight
ABSTRACT:
SUBMITTER: Inoue R
PROVIDER: S-EPMC8304653 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
The Feasibility and Applicability of Stem Cell Therapy for the Cure of Type 1 Diabetes.
Inoue Ryota R Nishiyama Kuniyuki K Li Jinghe J Miyashita Daisuke D Ono Masato M Terauchi Yasuo Y Shirakawa Jun J
Cells 20210624 7
Stem cell therapy using islet-like insulin-producing cells derived from human pluripotent stem cells has the potential to allow patients with type 1 diabetes to withdraw from insulin therapy. However, several issues exist regarding the use of stem cell therapy to treat type 1 diabetes. In this review, we will focus on the following topics: (1) autoimmune responses during the autologous transplantation of stem cell-derived islet cells, (2) a comparison of stem cell therapy with insulin injection ...[more]
Similar Datasets
Project description: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.
| S-EPMC3667565 | biostudies-literature
Project description:Islet transplantation is an important option in the treatment of type 1 diabetes. However, a donor shortage and immunosuppressant-related complications are the current major hurdles of islet transplantation. In this review, we discuss recent updates on islet transplantation to overcome these current obstacles and we share our perspectives on future β cell replacement therapy.
| S-EPMC9623521 | biostudies-literature
Project description:ObjectiveA number of clinical trials are underway to test whether mesenchymal stem cells (MSCs) are effective in treating various diseases, including type 1 diabetes. Although this cell therapy holds great promise, the optimal source of MSCs has yet to be determined with respect to major histocompatibility complex matching. Here, we examine this question by testing the ability of congenic MSCs, obtained from the NOR mouse strain, to reverse recent-onset type 1 diabetes in NOD mice, as well as determine the immunomodulatory effects of NOR MSCs in vivo.Research design and methodsNOR MSCs were evaluated with regard to their in vitro immunomodulatory function in the context of autoreactive T-cell proliferation and dendritic cell (DC) generation. The in vivo effect of NOR MSC therapy on reversal of recent-onset hyperglycemia and on immunogenic cell subsets in NOD mice was also examined.ResultsNOR MSCs were shown to suppress diabetogenic T-cell proliferation via PD-L1 and to suppress generation of myeloid/inflammatory DCs predominantly through an IL-6-dependent mechanism. NOR MSC treatment of experimental type 1 diabetes resulted in long-term reversal of hyperglycemia, and therapy was shown to alter diabetogenic cytokine profile, to diminish T-cell effector frequency in the pancreatic lymph nodes, to alter antigen-presenting cell frequencies, and to augment the frequency of the plasmacytoid subset of DCs.ConclusionsThese studies demonstrate the inimitable benefit of congenic MSC therapy in reversing experimental type 1 diabetes. These data should benefit future clinical trials using MSCs as treatment for type 1 diabetes.
| S-EPMC2992776 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance (IR) and impaired insulin secretion. The chronic inflammatory process contributed to IR and could also hamper pancreatic ? cell function. However, currently applied treatment cannot reverse ? cell damage or alleviate inflammation. Mesenchymal stem cells (MSCs), the cell-based therapy for their self-renewable, differentiation potential, and immunosuppressive properties, have been demonstrated in displaying therapeutic effects in T2DM. Adipose-derived MSCs (AD-MSCs) attracted more attention due to less harvested inconvenience and ethical issues commonly accompany with bone marrow-derived MSCs (BM-MSCs) and fetal annex-derived MSCs. Both AD-MSC therapy studies and mechanism explorations in T2DM animals presented that AD-MSCs could translate to clinical application. However, hyperglycemia, hyperinsulinemia, and metabolic disturbance in T2DM are crucial for impairment of AD-MSC function, which may limit the therapeutical effects of MSCs. This review focuses on the outcomes and the molecular mechanisms of MSC therapies in T2DM which light up the hope of AD-MSCs as an innovative strategy to cure T2DM.
| S-EPMC6712852 | biostudies-literature
Project description:In this review, we present (1) a brief discussion of hematopoietic stem cell transplantation (HSCT) for severe and refractory autoimmune diseases (AIDs) from its beginning in 1996 through recently initiated prospective randomized clinical trials; (2) an update (up to July 2009) of clinical and laboratory outcomes of 23 patients with newly diagnosed type 1 diabetes mellitus (T1DM), who underwent autologous HSCT at the Bone Marrow Transplantation Unit of the Ribeirão Preto Medical School, University of São Paulo, Brazil; (3) a discussion of possible mechanisms of action of HSCT in AIDs, including preliminary laboratory data obtained from our patients; and (4) a discussion of future perspectives of stem cell therapy for T1DM and type 2 DM, including the use of stem cell sources other than adult bone marrow and the combination of cell therapy with regenerative compounds.
| S-EPMC4089753 | biostudies-literature
Project description:RATIONALE, AIMS AND OBJECTIVES: Type 2 diabetes (T2D) is an archetypical chronic condition of significant prevalence. Yet the concept of cure in the context of T2D reveals an interplay between the medical imagination and clinical realities that can shift the course of a patient's care. There are two domains in which cure is sociologically constructed: the professional domain occupied by clinicians treating people with T2D, and the lay domain occupied by T2D patients. Lay epistemologies of cure tend to be focused on modifying the experience of having T2D, while professional epistemologies tend to focus on modifying the disease through medical treatment. The objective of this study is to explore the role of the concept of cure in the context of type 2 diabetes, a model for chronic disease.MethodsThrough surveys and interviews of T2D patients, providers and researchers at an urban academic medical centre, I explore the perspectives and attitudes each group have towards the concept of cure in T2D. Semi-structured interviews of T2D professionals and patient surveys consisting of free response questions and Likert scale items were thematically analysed for perspectives on cure in T2D.ResultsSixteen T2D patients met inclusion criteria and consented to the survey and ten T2D professionals were interviewed. Cure is conceived of heterogeneously both within and between epistemologies. Patients carry hopes of cure predicated on eliminating the unpleasant experiences of T2D and its treatments, while T2D professionals tend to avoid invoking the concept of cure, at least to patients, on grounds of clinical uncertainty. However, the concept of cure is a significant motivator of treatment in both lay and professional epistemologies.ConclusionDifferent viewpoints on cure in T2D present an opportunity for shared meaning and decision making between patients and their providers that can frame the best possible outcome for patient care.
| S-EPMC9303532 | biostudies-literature
Project description:Allogeneic hematopoietic stem cell transplantation has been well established for several decades as gene replacement therapy for patients with thalassemia major, and now offers very high rates of cure for patients who have access to this therapy. Outcomes have improved tremendously over the last decade, even in high-risk patients. The limited data available suggests that the long-term outcome is also excellent, with a >90% survival rate, but for the best results, hematopoietic stem cell transplantation should be offered early, before any end organ damage occurs. However, access to this therapy is limited in more than half the patients by the lack of suitable donors. Inadequate hematopoietic stem cell transplantation services and the high cost of therapy are other reasons for this limited access, particularly in those parts of the world which have a high prevalence of this condition. As a result, fewer than 10% of eligible patients are actually able to avail of this therapy. Other options for curative therapies are therefore needed. Recently, gene correction of autologous hematopoietic stem cells has been successfully established using lentiviral vectors, and several clinical trials have been initiated. A gene editing approach to correct the β-globin mutation or disrupt the BCL11A gene to increase fetal hemoglobin production has also been reported, and is expected to be introduced in clinical trials soon. Curative possibilities for the major hemoglobin disorders are expanding. Providing access to these therapies around the world will remain a challenge.
| S-EPMC5286930 | biostudies-literature
Project description:BackgroundInsulin-producing cell clusters (IPCCs) have recently been generated in vitro from adipose tissue-derived stem cells (ASCs) to circumvent islet shortage. However, it is unknown how long they can survive upon transplantation, whether they are eventually rejected by recipients, and how their long-term survival can be induced to permanently cure type 1 diabetes. IPCC graft survival is critical for their clinical application and this issue must be systematically addressed prior to their in-depth clinical trials.Methodology/principal findingsHere we found that IPCC grafts that differentiated from murine ASCs in vitro, unlike their freshly isolated islet counterparts, did not survive long-term in syngeneic mice, suggesting that ASC-derived IPCCs have intrinsic survival disadvantage over freshly isolated islets. Indeed, β cells retrieved from IPCC syngrafts underwent faster apoptosis than their islet counterparts. However, blocking both Fas and TNF receptor death pathways inhibited their apoptosis and restored their long-term survival in syngeneic recipients. Furthermore, blocking CD40-CD154 costimulation and Fas/TNF signaling induced long-term IPCC allograft survival in overwhelming majority of recipients. Importantly, Fas-deficient IPCC allografts exhibited certain immune privilege and enjoyed long-term survival in diabetic NOD mice in the presence of CD28/CD40 joint blockade while their islet counterparts failed to do so.Conclusions/significanceLong-term survival of ASC-derived IPCC syngeneic grafts requires blocking Fas and TNF death pathways, whereas blocking both death pathways and CD28/CD40 costimulation is needed for long-term IPCC allograft survival in diabetic NOD mice. Our studies have important clinical implications for treating type 1 diabetes via ASC-derived IPCC transplantation.
| S-EPMC3247284 | biostudies-literature
Project description:There are few established easy-to-perform exercise protocols with evidence-based effects for individuals with type 2 diabetes (T2D). A unique exercise regimen, interval walking training (IWT), has been reported to be beneficial for improving metabolic function, physical fitness and muscle strength in adults of overall health. This pilot study aims to demonstrate descriptive statistics of IWT adherence and changes in various data before and after the intervention of IWT in adults with T2D, perform statistical hypothesis testing, and calculate effect sizes. We performed a single-arm interventional pilot study with IWT for 20 weeks. We enrolled 51 participants with T2D aged 20-80 years with glycohemoglobin (HbA1c) levels of 6.5-10.0% (48-86 mmol/mol) and a body mass index of 20-34 kg/m2, respectively. The target was 60 min/week of fast walking for 20 weeks. The participants visited the hospital and were examined at 4-week intervals during this period. Between the start of IWT and after 20 weeks, we measured and evaluated changes in glucose and lipid metabolism data, body composition, physical fitness, muscle strength, dietary calorie intake, and daily exercise calories. All included participants completed IWT, with 39% of them reaching the target length of fast walking over 1,200 minutes in 20 weeks. In the primary outcome, HbA1c levels, and in the secondary, lipid metabolism and body composition, no significant changes were observed except for high-density lipoprotein cholesterol (HDL-C) (from 1.4 mmol/L to 1.5 mmol/L, p = 0.0093, t-test). However, in the target achievement group, a significant increase in VO2 peak by 10% (from 1,682 mL/min to 1,827 mL/min, p = 0.037, t-test) was observed. Effect sizes were Cohen's d = 0.25 of HDL-C, -0.55 of triglyceride, and 0.24 of VO2 peak in the target achievement group, which were considered to be of small to medium clinical significance. These results could be solely attributed to IWT since there were no significant differences in dietary intake and daily life energy consumption before and after the study. IWT could be highly versatile and was suggested to have a positive effect on lipid metabolism and physical fitness. In future randomized controlled trial (RCT) studies, the detailed effects of IWT, focusing on these parameters, will be examined. Trial registration: This trial was registered with the Japanese University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR: Usefulness on interval walking training in patients with type 2 diabetes. 000037303).
| S-EPMC10194951 | biostudies-literature
Project description:Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are widely prevalent metabolic diseases with differing pathologies. T1DM manifests due to autoimmune destruction of the pancreatic beta cells, resulting in a diminished secretion of insulin. T2DM originates from a state of insulin resistance, resulting in hyperglycemia and reduction in beta cell mass. Both diseases can cause severe health consequences. Despite the globally increasing prevalence of both T1DM and T2DM there remains to be a medically defined cure for either of these diseases. Recently, mesenchymal stem cells (MSCs) have been proposed as a possible curative treatment method. In this review, we explain the molecular mechanisms underlying MSCs and their potential ability to treat T1DM and T2DM. We describe the capability of MSCs to differentiate into insulin-producing cells and regenerate pancreatic beta cells, as well as assess their role in modulating the immune system. Lastly, we evaluate the current literature focusing on the clinical application of MSC transplantation in T1DM and T2DM. Despite the favorable results, study designs and analyses cast doubt on the effectiveness of MSCs for the management of T1DM. Conversely, the positive metabolic effects consistently demonstrated in the literature offer hope for MSCs as a treatment for T2DM, at least in the short-term.
| S-EPMC6261870 | biostudies-literature