ABSTRACT
The potential for amniotic fluid stem cell (AFSC) treatment to inhibit the progression of fibrotic lung injury has not been described. We have previously demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney injury through modification of the cytokine environment. Fibrotic lung injury, such as in Idiopathic Pulmonary Fibrosis (IPF), is mediated through pro-fibrotic and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment might inhibit the progression of bleomycin-induced pulmonary fibrosis through cytokine modulation. In particular, we aimed to investigate the effect of AFSC treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased in human IPF patients and is correlated with poor prognoses, advanced disease states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given at acute (day 0) or chronic (day 14) intervention time-points after bleomycin injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen deposition and preserved pulmonary function. CCL2 expression increased in bleomycin-injured bronchoalveolar lavage (BAL), but significantly decreased following AFSC treatment at either day 0 or at day 14. AFSC were observed to localize within fibrotic lesions in the lung, showing preferential targeting of AFSC to the area of fibrosis. We also observed that MMP-2 was transiently increased in BAL following AFSC treatment. Increased MMP-2 activity was further associated with cleavage of CCL2, rendering it a putative antagonist for CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction in BAL following AFSC treatment. Based on this data, we concluded that AFSC have the potential to inhibit the development or progression of fibrosis in a bleomycin injury model during both acute and chronic remodeling events.
Subject(s)
Amniotic Fluid/cytology , Bronchoalveolar Lavage , Chemokine CCL2/metabolism , Pulmonary Fibrosis/metabolism , Stem Cells/metabolism , Alveolar Epithelial Cells/metabolism , Animals , Bleomycin/adverse effects , Chemotaxis/immunology , Coculture Techniques , Cytokines/metabolism , Disease Models, Animal , Disease Progression , Female , Fetus , Humans , Inflammation Mediators/metabolism , Lung/metabolism , Lung/pathology , Lung/physiopathology , Male , Matrix Metalloproteinase 2/metabolism , Mice , Models, Biological , Pregnancy , Proteolysis , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/therapy , Stem Cell Transplantation , Stem Cells/immunology , Time FactorsABSTRACT
It is widely assumed that monkeys see a stranger in the mirror, whereas apes and humans recognize themselves. In this study, we question the former assumption by using a detailed comparison of how monkeys respond to mirrors versus live individuals. Eight adult female and six adult male brown capuchin monkeys (Cebus apella) were exposed twice to three conditions: (i) a familiar same-sex partner, (ii) an unfamiliar same-sex partner, and (iii) a mirror. Females showed more eye contact and friendly behavior and fewer signs of anxiety in front of a mirror than they did when exposed to an unfamiliar partner. Males showed greater ambiguity, but they too reacted differently to mirrors and strangers. Discrimination between conditions was immediate, and blind coders were able to tell the difference between monkeys under the three conditions. Capuchins thus seem to recognize their reflection in the mirror as special, and they may not confuse it with an actual conspecific. Possibly, they reach a level of self-other distinction intermediate between seeing their mirror image as other and recognizing it as self.
Subject(s)
Cebus/physiology , Discrimination, Psychological , Recognition, Psychology , Self Concept , Analysis of Variance , Animals , Empathy , Female , Male , Observation , Sex FactorsABSTRACT
The nigrostriatal system is critical for fine motor function and its deterioration during aging is thought to underlie the decline in fine manual ability of old persons. Because estrogen has a neuroprotective effect on this system, one might expect women's motor function to be less vulnerable to the detrimental effects of aging than that of men. We examined this hypothesis in the rhesus monkey, which has been established as an excellent model of human age-related motor impairment. We tested 28 young and old rhesus monkeys of both sexes in a task involving the retrieval of a Life Saver candy from rods of different complexity to determine whether fine motor ability (1) is sexually dimorphic, (2) declines with age and (3) declines differently in males and females. In addition, we measured the whole brain volume, the volumes of the caudate, putamen, hippocampal formation and the area of the corpus callosum in a subset of the monkeys (n=15) for which magnetic resonance images of the brain were available. All monkeys performed similarly in the test with the simplest rod. In the test with complex rods; however, age-related slowing of motor function was evident in males, but not in females. Age-related decreases in the normalized caudate and putamen volumes were similar in males and in females. In addition, motor speed was not significantly correlated to any of the neuroanatomical measures under study. Further studies will be necessary to uncover the neurohormonal bases of the differential age-related motor decline between males and females.
