Bone marrow mesenchymal stromal cells rescue cardiac function in streptozotocin-induced diabetic rats

Monnerat, Gustavo; Trentin-Sonoda, Mayra; Guerra, Bárbara; Manso, Gabriel; Ferreira, Andrea Cláudia Freitas; Silva, Diorney L S G; Coutinho, Danielle Carvalho Oliveira; Carneiro‐Ramos, Marcela Sorelli; Rodrigues, Deivid C.; Cabral-da-Silva, Mauricio Castro; Goldenberg, Regina Coeli dos Santos; Nascimento, José; Carvalho, Antônio Carlos Campos de; Medei, Emiliano

doi:10.1016/j.ijcard.2013.12.013

Cited by 15 publications

(38 citation statements)

References 41 publications

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“…ECG recording was carried out in conscious animals with a noninvasive method65. Electrodes were positioned in the DI lead and connected by flexible cables to a differential AC amplifier (model 1700, A-M Systems, USA), with signal low-pass filtered at 500 Hz and digitized at 1 kHz by a 16-bit A/D converter (Minidigi 1-D, Axon Instruments, USA) using Axoscope 9.0 software (Axon Instruments, USA).…”

Section: Methodsmentioning

confidence: 99%

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

et al. 2016

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Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity. IL-1β-induced spontaneous contractile events are associated with CaMKII oxidation and phosphorylation. We further show that DM-induced arrhythmias can be successfully treated by inhibiting the IL-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1β as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.

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Section: Methodsmentioning

confidence: 99%

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

et al. 2016

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“…4-Finally in the facts that the diminished autophagy in type 1 diabetes is an adaptive response that limits cardiac injury in type 1 diabetes, the cardioprotective effects of MScs, PIO and/or Ex-4 on the diabetic heart may not necessarily be mediated by autophagy. Instead, have several action other than modulation of autophagy and both of PIO and MSCs may protect the diabetic heart through other mechanisms including improving insulin signaling, fat oxidation, and anti-apoptotic and anti-oxidant properties [2,[11][12][13]. Despite the issues raised, the article by Prof Wassef et al [1] ''A comparison of mitochondrial dysfunction, cardiomyopathy analysis to detect protective effects MSCs, PIO and EX-4 '' is definitely of great value and certainly contributes to the course of diabetic heart disease.…”

Section: Increasing Expression Of Beclin-b and Lc3b-ii May Not Necessar-mentioning

confidence: 99%

Comments to the Editor Concerning the Paper Entitled “Mitochondrial Dysfunction in Diabetic Cardiomyopathy: Eﬀect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4” Mohamed Abd Elaziz Wassef et al.

Hamza

2017

Exp Clin Endocrinol Diabetes

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“…Streptozotocin (STZ) is frequently used to induce DM in rats. STZ induces beta cell destruction, leading to type 1 DM [4]. In STZ-induced diabetic rats, thyroid function is affected, leading to low thyroperoxidase (TPO) activity, with consequent reduction of serum thyroid hormones (TH) levels [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, insulin therapy is often unable to prevent all the long-term complications of DM [8]. Therefore, therapeutic options have been studied aiming to assist or even substitute insulin therapy, including cell therapy with mesenchymal stem cells (MSC) [4].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have shown that MSC therapy can be useful for the treatment of complications associated with DM, including cardiovascular complications, diabetic kidney disease and diabetic retinopathy [4,[9][10][11]. However, to our knowledge, the impact of MSC therapy on thyroid H 2 O 2 generation and thyroid function in DM remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Influence of Stem Cell Therapy on Thyroid Function and Reactive Oxygen Species Production in Diabetic Rats

Silva

Freitas

Monnerat³

et al. 2018

Horm Metab Res

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Cell therapy with mesenchymal stem cells (MSC) has been proposed for the treatment of diabetes mellitus (DM). It is known that the prevalence of thyroid disease is higher among diabetic patients than in general population. Therefore, our aim was to investigate the effect of the treatment with MSC on thyroid function and ROS generation in an experimental model of type 1 DM. Adult male Wistar rats were divided into the following groups: control, DM (80 mg/kg BW streptozotocin, iv.) and DM+MSC. MSC treatment occurred 4 weeks after DM induction and the animals were euthanized 4 weeks after MSC administration. We also evaluated the effect of co-culture with MSC or extracellular vesicles (EV) obtained from these cells on the rat thyroid cell line PCCL3 exposed to high glucose. Thyroid HO generation was increased in DM, which was reversed by MSC treatment. These changes paralled a significant DuOx1 mRNA increase. The incubation of PCCL3 with high glucose increased extracellular HO generation, which was reversed by both the co-culture with MSC and EV. Even though MSC treatment normalized thyroid ROS generation, serum thyroid hormone (TH) concentration remained low, along with increased serum TSH concentrations. Thyroperoxidase (TPO) activity, was reduced in DM, and MSC treatment did not normalize TPO. Therefore, we conclude that the treatment with MSC was able to reverse the increased thyroid HO generation in diabetic animals and in PCCL3 cells exposed to high glucose, an effect probably mediated by EV produced by these cells, acting in a paracrine fashion.

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Bone marrow mesenchymal stromal cells rescue cardiac function in streptozotocin-induced diabetic rats

Cited by 15 publications

References 41 publications

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

Comments to the Editor Concerning the Paper Entitled “Mitochondrial Dysfunction in Diabetic Cardiomyopathy: Eﬀect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4” Mohamed Abd Elaziz Wassef et al.

Influence of Stem Cell Therapy on Thyroid Function and Reactive Oxygen Species Production in Diabetic Rats

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