RESUMEN
BACKGROUND: A single administration of mesenchymal stromal cells (MSCs) has been shown to reduce lung inflammation in experimental elastase-induced emphysema; however, effects were limited in terms of lung-tissue repair and cardiac function improvement. We hypothesized that two doses of MSCs could induce further lung and cardiovascular repair by mitigating inflammation and remodeling in a model of emphysema induced by multiple elastase instillations. We aimed to comparatively investigate the effects of one versus two doses of MSCs, administered 1 week apart, in a murine model of elastase-induced emphysema. METHODS: C57BL/6 mice were randomly divided into control (CTRL) and emphysema (E) groups. Mice in the E group received porcine pancreatic elastase (0.2 IU, 50 µL) intratracheally once weekly for four consecutive weeks; the CTRL animals received sterile saline (50 µL) using the same protocol. Three hours after the last instillation, the E group was further randomized to receive either saline (SAL) or murine MSCs (105 cells) intratracheally, in one or two doses (1 week apart). Fourteen days later, mice were euthanized, and all data analyzed. RESULTS: Both one and two doses of MSCs improved lung mechanics, reducing keratinocyte-derived chemokine and transforming growth factor-ß levels in lung homogenates, total cell and macrophage counts in bronchoalveolar lavage fluid (BALF), and collagen fiber content in airways and blood vessels, as well as increasing vascular endothelial growth factor in lung homogenates and elastic fiber content in lung parenchyma. However, only the two-dose group exhibited reductions in tumor necrosis factor-α in lung tissue, BALF neutrophil and lymphocyte count, thymus weight, and total cellularity, as well as CD8+ cell counts and cervical lymph node CD4+ and CD8+ T cell counts, as well as further increased elastic fiber content in the lung parenchyma and reduced severity of pulmonary arterial hypertension. CONCLUSIONS: Two doses of MSCs enhanced lung repair and improvement in cardiac function, while inducing T cell immunosuppression, mainly of CD8+ cells, in elastase-induced emphysema.
Asunto(s)
Sistema Cardiovascular/patología , Pulmón/patología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Enfisema Pulmonar/terapia , Cicatrización de Heridas , Animales , Líquido del Lavado Bronquioalveolar , Sistema Cardiovascular/fisiopatología , Colágeno/metabolismo , Elastina/biosíntesis , Femenino , Terapia de Inmunosupresión , Inflamación/patología , Mediadores de Inflamación/metabolismo , Pulmón/fisiopatología , Tejido Linfoide/patología , Ratones Endogámicos C57BL , Enfisema Pulmonar/patología , Enfisema Pulmonar/fisiopatologíaRESUMEN
Photodynamic therapy (PDT) and low level laser therapy (LLLT) may mutually improve the outcomes on the healing process of chronic wounds and other skin pathologies, through processes known to stimulate the proliferation of dermal cellular structures, as well as antimicrobial application. This study proposes the use of nanoemulsion containing aluminium phthalocyanine chloride (ClAlPc) as photosensitizer (PS), to establish the most appropriate protocol for photostimulation in human skin biopsies, associated to type I collagen and elastin production. The combined effect of PS and light (diode laser at 670 nm) at three different doses is compared to the effect of light itself at doses of 70, 140 and 700 mJ c cm-2 , 7 and 14 days after irradiation. Histological analysis reveals the increase in collagen and elastin, higher than 20%, 14 days after treatment with PS and light at 140 mJ c cm-2 . Higher doses of light promote an inhibitory effect, leading to tissue degradation. In addition, the expression levels of the enzymes MMP-2 and MMP-9 (Gelatinases A and B - participant in various processes including tumoral progression and wound healing) are detected by gelatin zymography, reinforcing the efficacy of the combined treatment with PS and light at the intermediate dose.
Asunto(s)
Terapia por Luz de Baja Intensidad , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Piel/patología , Piel/efectos de la radiación , Colágeno Tipo I/biosíntesis , Elastina/biosíntesis , Humanos , Técnicas In Vitro , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Cicatrización de HeridasRESUMEN
Atrophy of salivary glands may occur by ductal obstruction caused by calculus, infection or neoplastic processes, or as consequence of systemic diseases and aging. In the present work, we have used histochemical methods to study the expression of elastic and collagen fibers during experimental atrophy of the submandibular gland of mice. Glandular atrophy was accompanied by a rapid increase in collagen deposition in both septal and intralobular regions. The expression of elastic fibers was not significantly altered during atrophy: a discrete increase of elastic fibers was noted only around ductal structures. The results showed that experimental ductal obstruction is a useful in vivo model to study molecular events that take part in the remodeling of the extracellular matrix during atrophy of salivary glands.