CONTADOR MARTINEZ, DAVID ERNESTO

Preferred name

Main Affiliation

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

dcontador@udd.cl

ORCID

0000-0002-0383-214X

Scopus Author ID

8251610900

Goggle Scholar

https://scholar.google.com/citations?user=SPrF9yMAAAAJ&hl=es&oi=ao

Now showing 1 - 10 of 12

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Characterisation of an animal model of type 2 diabetes with potential application in the evaluation of new therapies for diabetic neuropathy
(2018)
EZQUER, EDUARDO MARCELO
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DE GREGORIO CONCHA, CRISTIAN ALEJANDRO
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CONTADOR MARTINEZ, DAVID ERNESTO
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Daniela Santapau
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Campero, M
4
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Status and Trends of Physical Activity Surveillance, Policy, and Research in 164 Countries: Findings From the Global Observatory for Physical Activity—GoPA! 2015 and 2020 Surveys
(2023)
Andrea Ramírez Varela
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Pedro C. Hallal
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Juliana Mejía Grueso
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Željko Pedišić
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Deborah Salvo
<jats:p><jats:italic><jats:bold>Background</jats:bold>:</jats:italic> Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries. <jats:italic><jats:bold>Methods</jats:bold>:</jats:italic> We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years. <jats:italic><jats:bold>Results</jats:bold>:</jats:italic> The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world’s population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world’s population live in countries where PA promotion capacity should be significantly improved. <jats:italic><jats:bold>Conclusion</jats:bold>:</jats:italic> Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion.</jats:p>
1 2Scopus© Citations 46
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Dexamethasone and rosiglitazone are sufficient and necessary for producing functional adipocytes from mesenchymal stem cells
(2015)
CONTADOR MARTINEZ, DAVID ERNESTO
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EZQUER, EDUARDO FERNANDO
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Maximiliano Espinosa
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Martha Arango-Rodriguez
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Carlos Puebla
<jats:p> The final product of adipogenesis is a functional adipocyte. This mature cell acquires the necessary machinery for lipid metabolism, loses its proliferation potential, increases its insulin sensitivity, and secretes adipokines. Multipotent mesechymal stromal cells have been recognized as a source of adipocytes both in vivo and in vitro. The in vitro adipogenic differentiation of human MSC (hMSC) has been induced up to now by using a complex stimulus which includes dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin, and insulin (a classical cocktail) and evaluated according to morphological changes. The present work was aimed at demonstrating that the simultaneous activation of dexamethasone’s canonical signaling pathways, through the glucocorticoid receptor and CCAAT-enhancer-binding proteins ( C/EBPs) and rosiglitazone through peroxisome proliferator-activated receptor gamma ( PPAR-gamma) is sufficient yet necessary for inducing hMSC adipogenic differentiation. It was also ascertained that hMSC exposed just to dexamethasone and rosiglitazone (D&R) differentiated into cells which accumulated neutral lipid droplets, expressed C/EBP-alpha, PPAR-gamma, aP2, lipoprotein lipase, acyl-CoA synthetase, phosphoenolpyruvate carboxykinase, adiponectin, and leptin genes but did not proliferate. Glucose uptake was dose dependent on insulin stimulus and high levels of adipokines were secreted (i.e. displaying not only the morphology but also expressing mature adipocytes’ specific genes and functional characteristics). This work has demonstrated that (i) the activating C/EBPs and PPAR-gamma signaling pathways were sufficient to induce adipogenic differentiation from hMSC, (ii) D&R producing functional adipocytes from hMSC, (iii) D&R induce adipogenic differentiation from mammalian MSC (including those which are refractory to classical adipogenic differentiation stimuli). D&R would thus seem to be a useful tool for MSC characterization, studying adipogenesis pathways and producing functional adipocytes. </jats:p>
1Scopus© Citations 57 1
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The Antidiabetic Effect of Mesenchymal Stem Cells Is Unrelated to Their Transdifferentiation Potential But to Their Capability to Restore Th1/Th2 Balance and to Modify the Pancreatic Microenvironment
(2012)
EZQUER, EDUARDO FERNANDO
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EZQUER, EDUARDO MARCELO
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CONTADOR MARTINEZ, DAVID ERNESTO
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Ricca, Micaela
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Simon, Valeska
1Scopus© Citations 151 2
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Characterization of diabetic neuropathy progression in a mouse model of type 2 diabetes mellitus
(2018)
DE GREGORIO CONCHA, CRISTIAN ALEJANDRO
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CONTADOR MARTINEZ, DAVID ERNESTO
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Mario Campero
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EZQUER, EDUARDO MARCELO
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EZQUER, EDUARDO FERNANDO
<jats:p>Diabetes mellitus (DM) is one of most frequent chronic diseases with an increasing incidence in most countries. Diabetic neuropathy (DN) is one of the earliest and main complications of diabetic patients, which is characterized by progressive, distal-to-proximal degeneration of peripheral nerves. The cellular and molecular mechanisms that trigger DN are highly complex, heterogeneous and not completely known. Animal models have constituted a valuable tool for understanding diabetes pathophysiology; however, the temporal course of DN progression in animal models of type 2 diabetes (T2DM) is not completely understood.</jats:p> <jats:p>In this work, we characterized the onset and progression of DN in BKS db/db mice, including the main functional and histological features observed in the human disease. We demonstrated that diabetic animals display a progressive sensory loss and electrophysiological impairments in early-to-mid phases of disease. Furthermore, we detected an early decrease in intraepidermal nerve fibers (IENF) density in 18-week-old diabetic mice, which is highly associated with sensory loss and constitutes a reliable marker of DN. Other common histological parameters of DN, like Schwann cells apoptosis and infiltration of CD3+ cells in the sciatic nerve, were altered in mid-to-late phases of disease.</jats:p> <jats:p>Our results support the general consensus that DN evolves from initial functional to late structural changes. This work aimed to characterize the progression of DN in a reliable animal model sharing the main human disease features, which is necessary to assess new therapies for this complex disease. Finally, we also aimed to identify an effective temporal window where these potential treatments could be successfully applied.</jats:p>
6 1Scopus© Citations 43
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Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes
(2016)
FLAVIA ALEJANDRA BRUNA
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CONTADOR MARTINEZ, DAVID ERNESTO
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CONGET MOLINA, PAULETTE ANDREA
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Benjamín Erranz
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Claudia L. Sossa
<jats:p>Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult’s BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult’s BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion.</jats:p>
1Scopus© Citations 41 1
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Human adipose-derived mesenchymal stem cell-conditioned medium ameliorates polyneuropathy and foot ulceration in diabetic BKS db/db mice
(2020)
DE GREGORIO CONCHA, CRISTIAN ALEJANDRO
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CONTADOR MARTINEZ, DAVID ERNESTO
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Cristian Acosta
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Diego Díaz
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Constanza Cárcamo
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Diabetic polyneuropathy (DPN) is the most common and early developing complication of diabetes mellitus, and the key contributor for foot ulcers development, with no specific therapies available.</jats:p> <jats:p>Different studies have shown that mesenchymal stem cell (MSC) administration is able to ameliorate DPN; however, limited cell survival and safety reasons hinder its transfer from bench to bedside. MSCs secrete a broad range of antioxidant, neuroprotective, angiogenic, and immunomodulatory factors (known as conditioned medium), which are all decreased in the peripheral nerves of diabetic patients. Furthermore, the abundance of these factors can be boosted in vitro by incubating MSCs with a preconditioning stimulus, enhancing their therapeutic efficacy. We hypothesize that systemic administration of conditioned medium derived from preconditioned MSCs could reverse DPN and prevent foot ulcer formation in a mouse model of type II diabetes mellitus.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Diabetic BKS <jats:italic>db/db</jats:italic> mice were treated with systemic administration of conditioned medium derived from preconditioned human MSCs; conditioned medium derived from non-preconditioned MSCs or vehicle after behavioral signs of DPN was already present. Conditioned medium or vehicle administration was repeated every 2 weeks for a total of four administrations, and several functional and structural parameters characteristic of DPN were evaluated. Finally, a wound was made in the dorsal surface of both feet, and the kinetics of wound closure, re-epithelialization, angiogenesis, and cell proliferation were evaluated.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Our molecular, electrophysiological, and histological analysis demonstrated that the administration of conditioned medium derived from non-preconditioned MSCs or from preconditioned MSCs to diabetic BKS <jats:italic>db/db</jats:italic> mice strongly reverts the established DPN, improving thermal and mechanical sensitivity, restoring intraepidermal nerve fiber density, reducing neuron and Schwann cell apoptosis, improving angiogenesis, and reducing chronic inflammation of peripheral nerves. Furthermore, DPN reversion induced by conditioned medium administration enhances the wound healing process by accelerating wound closure, improving the re-epithelialization of the injured skin and increasing blood vessels in the wound bed in a skin injury model that mimics a foot ulcer.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Studies conducted indicate that MSC-conditioned medium administration could be a novel cell-free therapeutic approach to reverse the initial stages of DPN, avoiding the risk of lower limb amputation triggered by foot ulcer formation and accelerating the wound healing process in case it occurs.</jats:p> </jats:sec>
1Scopus© Citations 79 4
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Human renal adipose tissue induces the invasion and progression of renal cell carcinoma
(2017)
Peng Liu
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Zhipeng Wang
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Sarah Brown
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Vinodh Kannappan
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Patricia Erebi Tawari
1Scopus© Citations 21 1
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Administration of secretome derived from human mesenchymal stem cells prevents diabetic neuropathy progression in an animal model of type 2 diabetes
(2019)
EZQUER, EDUARDO FERNANDO
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DE GREGORIO CONCHA, CRISTIAN ALEJANDRO
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CONTADOR MARTINEZ, DAVID ERNESTO
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Campero, M.
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Santapau, D
2
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Renal peritumoral adipose tissue undergoes a browning process and stimulates the expression of epithelial-mesenchymal transition markers in human renal cells
(2022)
Matías Ferrando
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Flavia Alejandra Bruna
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Leonardo Rafael Romeo
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CONTADOR MARTINEZ, DAVID ERNESTO
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Daiana Lorena Moya-Morales
<jats:title>Abstract</jats:title><jats:p>Tumor cells can interact with neighboring adipose cells and adipocyte dedifferentiation appears to be an important aspect of tumorigenesis. We evaluated the size of adipocytes in human adipose explants from normal (hRAN) and kidney cancer (hRAT); changes in the expression of WAT and BAT/beige markers in hRAN and hRAT; the expression of epithelial-mesenchymal transition (EMT) cell markers in human kidney tumor (786-O, ACHN and Caki-1); and non-tumor (HK-2) epithelial cell lines incubated with the conditioned media (CMs) of hRAN and hRAT. We observed that hRAT adipocytes showed a significantly minor size compared to hRAN adipocytes. Also, we observed that both Prdm16 and Tbx1 mRNA and the expression of UCP1, TBX1, PPARγ, PCG1α, c/EBPα LAP and c/EBPα LIP was significantly higher in hRAT than hRAN. Finally, we found an increase in vimentin and N-cadherin expression in HK-2 cells incubated for 24 h with hRAT-CMs compared to hRAN- and control-CMs. Furthermore, desmin and N-cadherin expression also increased significantly in 786-O when these cells were incubated with hRAT-CMs compared to the value observed with hRAN- and control-CMs. We observed a significant decrease in E-cadherin expression in the ACHN cell line incubated with hRAT-CMs versus hRAN- and control-CMs. However, we did not observe changes in E-cadherin expression in HK-2, 786-O or Caki-1. The results obtained, together with the results previously published by our group, allow us to conclude that perirenal white adipose tissue browning contributes to tumor development in kidney cancer. In addition, hRAT-CMs increases the expression of mesenchymal markers in renal epithelial cells, which could indicate a regulation of EMT due to this adipose tissue. </jats:p>
1Scopus© Citations 11 1

CONTADOR MARTINEZ, DAVID ERNESTO

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