Secretome effect of adipose tissue-derived stem cells cultured two-dimensionally and three-dimensionally in mice with streptozocin induced type 1 diabetes

Dias, Isabelle; Pinheiro, Daphne; Silva, Karina Ribeiro; Stumbo, Ana Carolina; Thole, Alessandra Alves; Cortez, Erika; Carvalho, Laís de; Carvalho, Simone

doi:10.1016/j.crphar.2021.100069

Cited by 6 publications

(5 citation statements)

References 45 publications

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“…Male Swiss mice obtained from Charles River Laboratories (L’arbresle, France) were housed at constant temperature (20–22°C) and with a 12-h light–dark cycle. At the age of 2 mo, they received an intraperitoneal injection of STZ (40 mg/kg) diluted in citrate buffer (0.05 mmol/L, pH 4.5) for four consecutive days, as described previously[ 21 ]. A week later, mice receiving only citrate buffer (nondiabetic) and treated mice exhibiting blood glucose ≥ 300 mg/100 mL (STZ diabetic) were subdivided into four groups of eight males, with either free access to water (control) or a 0.5% Bza solution as drinking liquid (Bza-drinking) for 24 d. To measure plasma insulin levels at the beginning of treatment, blood samples were withdrawn from tail vein then centrifuged and analyzed using Ultrasensitive insulin-ELISA kit (Mercodia, Uppsala, Sweden).…”

Section: Methodsmentioning

confidence: 99%

“…More importantly, diabetic phenotypes of diverse animal models have been ameliorated when white adipose tissue (WAT) or brown adipose tissue (BAT) has been reintroduced in these models, irrespective of the method used. Nowadays, it is suggested that adipose tissue contributes to the correction of type 1 diabetes, since hyperglycemia was lowered in diabetic mice treated by conditioned media from adipose-derived stem cells[ 21 ], and since mitigation of diabetes was observed in STZ diabetic mice receiving BAT transplantation[ 19 ]. To date, the beneficial effects of ingested Bza on glucose and lipid handling have been studied in obese rodents only[ 1 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Hyperglycemia and reduced adiposity of streptozotocin-induced diabetic mice are not alleviated by oral benzylamine supplementation

Carpéné¹,

Atanasov²,

Les³

et al. 2022

WJD

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BACKGROUND Benzylamine (Bza) oral administration delays the onset of hyperglycemia in insulin-resistant db -/- mice; a genetic model of obesity and type 2 diabetes. AIM To extend the antihyperglycemic properties of oral benzylamine to a model of insulin-deficient type 1 diabetes. METHODS Male Swiss mice were rendered diabetic by streptozotocin treatment (STZ) and divided in two groups: one received 0.5% Bza as drinking solution for 24 d (STZ Bza-drinking) while the other was drinking water ad libitum . Similar groups were constituted in age-matched, nondiabetic mice. Food intake, liquid intake, body weight gain and nonfasting blood glucose levels were followed during treatment. At the end of treatment, fasted glycemia, liver and white adipose tissue (WAT) mass were measured, while glucose uptake assays were performed in adipocytes. RESULTS STZ diabetic mice presented typical features of insulin-deficient diabetes: reduced body mass and increased blood glucose levels. These altered parameters were not normalized in the Bza-drinking group in spite of restored food and water intake. Bza consumption could not reverse the severe fat depot atrophy of STZ diabetic mice. In the nondiabetic mice, no difference was found between control and Bza-drinking mice for any parameter. In isolated adipocytes, hexose uptake was partially activated by 0.1 mmol/L Bza in a manner that was obliterated in vitro by the amine oxidase inhibitor phenelzine and that remained unchanged after Bza supplementation. Oxidation of 0.1 mmol/L Bza in WAT was lower in STZ diabetic than in normoglycemic mice. CONCLUSION Bza supplementation could not normalize the altered glucose handling of STZ diabetic mice with severe WAT atrophy. Consequently, its antidiabetic potential in obese and diabetic rodents does not apply to lipoatrophic type 1 diabetic mice.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hyperglycemia and reduced adiposity of streptozotocin-induced diabetic mice are not alleviated by oral benzylamine supplementation

Carpéné¹,

Atanasov²,

Les³

et al. 2022

WJD

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“…Pdx1, a β‐cell marker, was increased in the 2D‐CM group, but this effect was not seen in the 3D‐CM. [ 107 ] In our previous study, content analysis was performed on CMs produced with UC‐MSCs cultured in 2D and 3D environments before examining their in vivo therapeutic effects. Scaffolds were used for the 3D culture, and the cells were grown following a specific topography.…”

Section: Therapeutic Effects Of Msc‐cm On Diabetes and Related Compli...mentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stem Cell‐Derived Conditioned Medium for Diabetes Mellitus and Related Complications

Isildar,

Ozkan,

Koyuturk

2023

Advanced Therapeutics

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Diabetes mellitus (DM) is one of the most life‐threatening metabolic disorders, with 9% of the global prevalence, and it was estimated to be rising to 12.2% in 2045. Currently, there is no definitive treatment for DM. Although life‐saving, insulin administration to control blood sugar is not a cure for DM and is insufficient to prevent DM‐related complications such as nephropathy, neuropathy, or retinopathy. For this reason, studies are continuing to develop treatments that will provide β‐cell regeneration while suppressing autoimmunity. Mesenchymal stem cells (MSCs) are multipotent stem cells with a high proliferation capacity, immunosuppression, and immunomodulation ability. MSCs have gained therapeutic importance with these properties besides their differentiation ability. The immunosuppressive and immunomodulatory properties of the cells arise from the soluble and insoluble factors they secrete into the extracellular environment. Therefore, the culture medium where these cells grow has therapeutic value and is named conditioned medium (CM). In this context, CM obtained from MSCs could provide a similar therapeutic effect with fewer safety concerns. Furthermore, preconditioning of MSCs could improve the effectiveness of these cells and associated cellular products. So, this review summarizes the recent advances in MSC‐derived CMs and their therapeutic potential for DM and related complications.This article is protected by copyright. All rights reserved

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“…Here we aimed to compare the secretomes of AT-MSCs, BM-MSCs, gingiva-derived MSCs (G-MSCs), placenta-derived MSCs (PL-MSCs), and umbilical cord-derived MSCs (UC-MSCs) cultured as monolayers (2D) and as cell spheroids (3D), since there is evidence that culturing conditions also have an impact on the cells' secretome 22 . We have analyzed the expression of 41 cytokines and growth factors in the CM samples taken on the 3rd day of culturing and assessed the MSCs-derived CM effect on macrophages polarization in vitro.…”

Section: Introductionmentioning

confidence: 99%

MSCs’ conditioned media cytokine and growth factor profiles and their impact on macrophage polarization

Peshkova

Корнеев

Сулейманов

et al. 2023

Preprint

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Background. There is a growing body of evidence that multipotent mesenchymal stromal cells’ (MSCs’) remarkable therapeutic potential is attributed not only to their differentiation and regenerative capacity, but also to the paracrine effect, underlying their immunomodulatory properties. MSCs’ secretome (i.e., cytokines, growth factors, and extracellular vesicles) is therefore increasingly discussed in the context of their ability to modulate inflammatory response and promote regeneration. There is evidence that 2D or 3D culturing conditions have an impact on the cells’ secretome, and here we aimed to compare the secretion of cytokines and growth factors in human MSCs from different sources cultured in 2D and 3D conditions and assess their effect on human macrophages polarization in vitro. Methods. MSCs were derived from human adipose tissue, bone marrow, gingiva, placenta, and umbilical cord, cultured as monolayers or as cell spheroids. Their cytokine profiles were analyzed, and data standardization was carried out using a z-score. Human peripheral blood mononuclear cells-derived macrophages were then treated with umbilical cord-derived MSCs’ conditioned media and their effect on macrophages polarization was assessed. Results. Our findings suggest that umbilical cord-derived MSCs’ conditioned media demonstrated the highest cytokine and growth factor levels and despite mostly pro-inflammatory cytokine profile were able to promote human macrophages’ polarization to anti-inflammatory M2 state and inhibit their polarization to pro-inflammatory M1 state. Conclusions. Umbilical cord-derived MSCs’ conditioned media hold great potential for therapeutic use, demonstrating significant anti-inflammatory effect on human macrophages.

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Secretome effect of adipose tissue-derived stem cells cultured two-dimensionally and three-dimensionally in mice with streptozocin induced type 1 diabetes

Cited by 6 publications

References 45 publications

Hyperglycemia and reduced adiposity of streptozotocin-induced diabetic mice are not alleviated by oral benzylamine supplementation

Hyperglycemia and reduced adiposity of streptozotocin-induced diabetic mice are not alleviated by oral benzylamine supplementation

Therapeutic Potential of Mesenchymal Stem Cell‐Derived Conditioned Medium for Diabetes Mellitus and Related Complications

MSCs’ conditioned media cytokine and growth factor profiles and their impact on macrophage polarization

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