Browsing by Author "Carpio, Daniel"
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Item Human adipose-derived mesenchymal stem cell-conditioned medium ameliorates polyneuropathy and foot ulceration in diabetic BKS db/db mice(2020) Gregorio, Cristian De; Contador, David; Díaz, Diego; Cárcamo, Constanza; Santapau, Daniela; Lobos-González, Lorena; Acosta, Cristian; Campero, Mario; Carpio, Daniel; Gabriele, Caterina; Gaspari, Marco; Aliaga-Tobar, Víctor; Maracaja-Coutinho, Vinicius; Ezquer, Marcelo; Ezquer, FernandoBackground: 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. 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. Methods: Diabetic BKS db/db 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. Results: 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 db/db 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. Conclusions: 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.Item Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus.(Fernando Ezquer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., 2015) Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette; Ezquer, MarceloThe aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected.Item Recomendaciones sobre el manejo del compromiso renal del lupus eritematoso sistémico. Documento de Consenso de las Sociedades Chilenas de Nefrología y Reumatología(Sociedad Medica de Santiago, 2015) Aguirre, Verónica; Alvo, Miriam; Ardiles, Leopoldo; Carpio, Daniel; Foster, Carolina; Goecke, Annelise; Jalil, Roberto; Massardo, Loreto; Palma, Sergio; Roessler, Emilio; Wurgaft, AndrésRenal involvement affects over one half of patients with Systemic Lupus Erythematosus increasing their mortality and morbidity, including chronic renal disease and the need of renal replacement therapies. Aiming to achieve a consensus in the most relevant topics on diagnosis, therapy and follow-up of patients with lupus renal disease, the Chilean Societies of Nephrology and Rheumatology constituted a workgroup that, based on a critical review of the available literature and their experience, raised and answered by consensus a set of relevant questions. This document includes aspects related to the clinical diagnosis, the importance of a suitable histological classification, therapeutic alternatives to induce and maintain disease remission, strategies for follow-up, additional therapies and gynecological-obstetric issues.