Stem cell therapy for diabetes mellitus.
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ABSTRACT:
SUBMITTER: Voltarelli JC
PROVIDER: S-EPMC4089753 | biostudies-literature | 2011 Sep
REPOSITORIES: biostudies-literature
Publications
Stem cell therapy for diabetes mellitus.
Voltarelli Júlio C JC Couri Carlos E B CE Oliveira Maria C MC Moraes Daniela A DA Stracieri Ana B P L AB Pieroni Fabiano F Barros George M N GM Malmegrim Kelen C R KC Simões Belinda P BP Leal Angela M O AM Foss Milton C MC
Kidney international supplements 20110901 3
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, Universi ...[more]
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Project description:BackgroundStem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM.Methods and findingsWe pooled participant-level data from twenty-two eligible clinical trials that satisfied our inclusion criteria, with a total of 524 patients. There were significant differences in the outcome based on the type and source of the infused cells. Out of all T1DM patients who received CD34+ hematopoietic stem cell (HSC) infusion, 58.9% became insulin independent for a mean period of 16 months, whereas the results were uniformly negative in patients who received umbilical cord blood (UCB). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) provided significantly beneficial outcome in T1DM, when compared to bone-marrow mesenchymal stem cells (BM-MSCs) (P<0.0001 and P = 0.1557). Administration of stem cell therapy early after DM diagnosis was more effective than intervention at later stages (relative risk = 2.0, P = 0.0008). Adverse effects were observed in only 21.72% of both T1DM and T2DM stem cell recipients with no reported mortality. Out of all poor responders, 79.5% were diagnosed with diabetic ketoacidosis.ConclusionsStem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34+ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy.
| S-EPMC4830527 | biostudies-literature
Project description:Since its introduction more than twenty years ago, intraportal allogeneic cadaveric islet transplantation has been shown to be a promising therapy for patients with Type I Diabetes (T1D). Despite its positive outcome, the impact of islet transplantation has been limited due to a number of confounding issues, including the limited availability of cadaveric islets, the typically lifelong dependence of immunosuppressive drugs, and the lack of coverage of transplant costs by health insurance companies in some countries. Despite improvements in the immunosuppressive regimen, the number of required islets remains high, with two or more donors per patient often needed. Insulin independence is typically achieved upon islet transplantation, but on average just 25% of patients do not require exogenous insulin injections five years after. For these reasons, implementation of islet transplantation has been restricted almost exclusively to patients with brittle T1D who cannot avoid hypoglycemic events despite optimized insulin therapy. To improve C-peptide levels in patients with both T1 and T2 Diabetes, numerous clinical trials have explored the efficacy of mesenchymal stem cells (MSCs), both as supporting cells to protect existing β cells, and as source for newly generated β cells. Transplantation of MSCs is found to be effective for T2D patients, but its efficacy in T1D is controversial, as the ability of MSCs to differentiate into functional β cells in vitro is poor, and transdifferentiation in vivo does not seem to occur. Instead, to address limitations related to supply, human embryonic stem cell (hESC)-derived β cells are being explored as surrogates for cadaveric islets. Transplantation of allogeneic hESC-derived insulin-producing organoids has recently entered Phase I and Phase II clinical trials. Stem cell replacement therapies overcome the barrier of finite availability, but they still face immune rejection. Immune protective strategies, including coupling hESC-derived insulin-producing organoids with macroencapsulation devices and microencapsulation technologies, are being tested to balance the necessity of immune protection with the need for vascularization. Here, we compare the diverse human stem cell approaches and outcomes of recently completed and ongoing clinical trials, and discuss innovative strategies developed to overcome the most significant challenges remaining for transplanting stem cell-derived β cells.
| S-EPMC7953062 | biostudies-literature
Project description:As a novel cell-free strategy, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) inherit the therapeutic potential of donor cells, and are widely used for the treatment of many diseases. Increasing studies have shown that MSC-EVs transfer various bioactive molecules to create a beneficial microenvironment, thus exerting protective roles in diabetic mellitus (DM) and diabetic complications. To overcome the limitations of natural MSC-EVs such as heterogeneity and insufficient function, several modification methods have been established for constructing engineered MSC-EVs with elevated repairing efficiency. In this review, the PubMed library was searched from inception to August 2022, using a combination of Medical Subject Headings (MeSH) and keywords related to MSC-EVs, DM, and diabetic complications. We provide an overview of the major characteristics of MSC-EVs and summarize the recent advances of MSC-EV-based therapy for hyperglycemia-induced tissue damage with an emphasis on MSC-EV-mediated delivery of functional components. Moreover, the potential applications of engineered MSC-EVs in DM-related diseases therapy are discussed by presenting examples, and the opportunities and challenges for the clinical translation of MSC-EVs, especially engineered MSC-EVs, are evaluated.
| S-EPMC9607185 | biostudies-literature
Project description:Diabetes mellitus (DM) is a chronic metabolic disease with high morbidity and mortality. Recently, stem cell-based therapy for DM has shown considerable promise. Here, we undertook a systematic review and meta-analysis of published clinical studies to evaluate the efficacy and safety of stem cell therapy for both type 1 DM (T1DM) and type 2 DM (T2DM). The PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and ClinicalTrials.gov databases were searched up to November 2018. We employed a fixed-effect model using 95% confidence intervals (CIs) when no statistically significant heterogeneity existed. Otherwise, a random-effects statistical model was used. Twenty-one studies met our inclusion criteria: ten T1DM studies including 226 patients and eleven T2DM studies including 386 patients. Stem cell therapy improved C-peptide levels (mean difference (MD), 0.41; 95% CI, 0.06 to 0.76) and glycosylated hemoglobin (HbA1c; MD, -3.46; 95% CI, -6.01 to -0.91) for T1DM patients. For T2DM patients, stem cell therapy improved C-peptide levels (MD, 0.33; 95% CI, 0.07 to 0.59), HbA1c (MD, -0.87; 95% CI, -1.37 to -0.37) and insulin requirements (MD, -35.76; 95% CI, -40.47 to -31.04). However, there was no significant change in fasting plasma glucose levels (MD, -0.52; 95% CI, -1.38 to 0.34). Subgroup analyses showed significant HbA1c and C-peptide improvements in patients with T1DM treated with bone marrow hematopoietic stem cells (BM-HSCs), while there was no significant change in the mesenchymal stem cell (MSC) group. In T2DM, HbA1c and insulin requirements decreased significantly after MSC transplantation, and insulin requirements and C-peptide levels were significantly improved after bone marrow mononuclear cell (BM-MNC) treatment. Stem cell therapy is a relatively safe and effective method for selected individuals with DM. The data showed that BM-HSCs are superior to MSCs in the treatment of T1DM. In T2DM, MSC and BM-MNC transplantation showed favorable therapeutic effects.
| S-EPMC6961772 | 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
Project description:BackgroundDiabetes mellitus is a major health concern in current scenario which has been found to affect people of almost all ages. The disease has huge impact on global health; therefore, alternate methods apart from insulin injection are being explored to cure diabetes. Therefore, this review mainly focuses on the current status and therapeutic potential of stem cells mainly mesenchymal stem cells (MSCs) for Type 1 diabetes mellitus in preclinical animal models as well as humans.MethodsCurrent treatment for Type 1 diabetes mellitus mainly includes use of insulin which has its own limitations and also the underlying mechanism of diseases is still not explored. Therefore, alternate methods to cure diabetes are being explored. Stem cells are being investigated as an alternative therapy for treatment of various diseases including diabetes. Few preclinical studies have also been conducted using undifferentiated MSCs as well as in vitro MSCs differentiated into β islet cells.ResultsThese stem cell transplant studies have highlighted the benefits of MSCs, which have shown promising results. Few human trials using stem cells have also affirmed the potential of these cells in alleviating the symptoms.ConclusionStem cell transplantation may prove to be a safe and effective treatment for patients with Type 1 diabetes mellitus.
| S-EPMC6250656 | biostudies-literature
Project description:Human term placenta and other postpartum-derived biological tissues are promising sources of perinatal cells with unique stem cell properties. Among the massive current research on stem cells, one medical focus on easily available stem cells is to exploit them in the design of immunotherapy protocols, in particular for the treatment of chronic non-curable human diseases. Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells and perinatal cells can be harnessed both to generate insulin-producing cells for beta cell replenishment and to regulate autoimmune mechanisms via immunomodulation capacity. In this study, the strong points of cells derived from amniotic epithelial cells and from umbilical cord matrix are outlined and their potential for supporting cell therapy development. From a basic research and expert stem cell point of view, the aim of this review is to summarize information regarding the regenerative medicine field, as well as describe the state of the art on possible cell therapy approaches for diabetes.
| S-EPMC9738084 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) are multipotent, self-renewing cells that can be found in almost all postnatal organs and tissues. The main functional characteristics of MSCs are their immunomodulatory ability, capacity for self-renewal, and differentiation into mesodermal tissues. The ability of MSCs to differentiate into several cell types, including muscle, brain, vascular, skin, cartilage, and bone cells, makes them attractive as therapeutic agents for a number of diseases including complications of diabetes mellitus. We review here the potential of MSCs as new therapeutic agents in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic polyneuropathy, diabetic retinopathy, and diabetic wounds. Also, in this review we discuss the current limitations for MSCs therapy in humans.
| S-EPMC3059410 | biostudies-literature
Project description:PurposeDiabetes mellitus erectile dysfunction (DMED) is a common resulting complication of diabetes. Studies have shown mesenchymal stem cell (MSC)-based therapy was beneficial in alleviating erectile function of DMED rats. While the pathogenesis of DMED and the mechanism MSCs actions are unclear.Materials and methodsWe constructed a rat model of DMED with or without intracavernous injection of MSCs, and performed microRNA (miRNA) sequencing of corpora cavernosa tissues.ResultsWe identified three overlapping differentially expressed miRNAs (rno-miR-1298, rno-miR-122-5p, and rno-miR-6321) of the normal control group, DMED group, and DMED+MSCs group. We predicted 285 target genes of three miRNAs through RNAhybrid and miRanda database and constructed a miRNA-target gene network through Cytoscape. Next, we constructed protein-protein interaction networks through STRING database and identified the top 10 hub genes with highest connectivity scores. Five GO terms including cellular response to growth factor stimulus (GO:0071363), ossification (GO:0001503), response to steroid hormone (GO:0048545), angiogenesis (GO:0001525), positive regulation of apoptotic process (GO:0043065), and one Reactome pathway (Innate Immune System) were significantly enriched by 10 hub genes using the Metascape database. We selected the GSE2457 dataset to validate the expression of hub genes and found only the expression of B4galt1 was statistically different (p<0.001). B4galt1 was highly expressed in penile tissues of diabetic rats and would be negatively regulated by rno-miR-1298.ConclusionsThree key miRNAs were identified in DMED rats with stem cell therapy and the miR-1298/B4GalT1 axis might exert function in stem cell therapy for ED.
| S-EPMC9482859 | biostudies-literature
Project description:BackgroundThis study explored the details of the immune response after autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1 diabetes mellitus.MethodsPeripheral blood mononuclear cells (PBMCs) from 18 patients with type 1 diabetes mellitus were taken at baseline and 12 months after AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T-helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in PBMC culture supernatants were assessed.ResultsCompared with patients receiving insulin-only treatment, the patients receiving AHSCT treatment showed better residual C-peptide secretion, lower anti-GAD titers and less exogenous insulin dosages after 12 months of follow-up. AHSCT treatment was associated with significantly reduced Th1 and Th17 cell proportions as well as decreased IFN-γ, IL-2, IL-12p40 and IL-17A levels in the PBMC culture supernatants (all P < 0.05). Although there was no significant Treg cell expansion after AHSCT treatment, we observed increased IL-10, TGF-β and Foxp3 mRNA expression and increased TGF-β levels. However, we found no significant changes in the T-cell subpopulations after insulin treatment, except for higher IL-12p40 mRNA expression and a lower proportion of Treg cells.ConclusionsAHSCT treatment was associated with decreased expansion and function of Th1 and Th17 cells, which may explain the better therapeutic effect of AHSCT compared with the traditional intensive insulin therapy.Trial registrationClinicaltrials.gov NCT00807651 . Registered 18 December 2008.
| S-EPMC5395765 | biostudies-literature