Background-Cardiac cell therapy for older patients who experience a myocardial infarction may require highly regenerative cells from young, healthy (allogeneic) donors. Bone marrow mesenchymal stem cells (MSCs) are currently under clinical investigation because they can induce cardiac repair and may also be immunoprivileged (suitable for allogeneic applications). However, it is unclear whether allogeneic MSCs retain their immunoprivilege or functional efficacy late after myocardial implantation. We evaluated the effects of MSC differentiation on the immune characteristics of cells in vitro and in vivo and monitored cardiac function for 6 months after post-myocardial infarction MSC therapy. Methods and Results-In the in vitro experiments, inducing MSCs to acquire myogenic, endothelial, or smooth muscle characteristics (via 5-azacytidine or cytokine treatment) increased major histocompatibility complex-Ia and -II (immunogenic) expression and reduced major histocompatibility complex-Ib (immunosuppressive) expression, in association with increased cytotoxicity in coculture with allogeneic leukocytes. In the in vivo experiments, we implanted allogeneic or syngeneic MSCs into infarcted rat myocardia. We measured cell differentiation and survival (immunohistochemistry, real-time polymerase chain reaction) and cardiac function (echocardiography, pressure-volume catheter) for 6 months. MSCs (versus media) significantly improved ventricular function for at least 3 months after implantation. Allogeneic (but not syngeneic) cells were eliminated from the heart by 5 weeks after implantation, and their functional benefits were lost within 5 months. Conclusions-The long-term ability of allogeneic MSCs to preserve function in the infarcted heart is limited by a biphasic immune response whereby they transition from an immunoprivileged to an immunogenic state after differentiation, which is associated with an alteration in major histocompatibility complex-immune antigen profile. (Circulation. 2010; 122:2419-2429.)Key Words: stem cells Ⅲ immune system Ⅲ myocardial infarction Ⅲ transplantation B one marrow mesenchymal stem cells (MSCs) have been widely investigated for their potential to prevent cardiac dysfunction after a myocardial infarction (MI). In preclinical studies conducted with young animals, implanted MSCs effectively restored ventricular function after acute or chronic MI. 1,2 The early clinical trials with aging patients demonstrated statistically significant, but comparatively limited, beneficial effects on ventricular volumes and ejection fraction when the patients received autologous MSCs. 3 This muted response was due largely to an age-related decrease in the regenerative capacity of the patients' cells, as demonstrated in studies that examined age-related changes in autologous progenitor cells. 4,5 A source of highly regenerative donor cells would thus dramatically advance the prevention of congestive heart failure in aged patients who have multiple comorbidities. Clinical Perspective on p 2429Allogeneic MSCs is...

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This paper reviews a way of investigating health and welfare problems in captive wild animals (e.g., those in zoos, aviaries, aquaria, or aquaculture systems) that has great potential, but to date has been little used: systematically comparing species with few or no health and welfare issues to those more prone to problems. Doing so empirically pinpoints species-typical welfare risk and protective factors (such as aspects of their natural behavioral biology): information which can then be used to help prevent or remedy problems by suggesting new ways to improve housing and husbandry, and by identifying species intrinsically best suited to captivity. We provide a detailed, step-by-step "how to" guide for researchers interested in using these techniques, including guidance on how to statistically control for the inherent similarities shared by related species: an important concern because simple, cross-species comparisons that do not do this may well fail to meet statistical assumptions of non-independence. The few relevant studies that have investigated captive wild animals' welfare problems using this method are described. Overall, such approaches reap value from the great number and diversity of species held in captivity (e.g., the many thousands of species held in zoos); can yield new insights from existing data and published results; render previously intractable welfare questions (such as "do birds need to fly?" or "do Carnivora need to hunt?") amenable to study; and generate evidence-based principles for integrating animal welfare into collection planning.

Captive parrots (Psittaciformes) commonly engage in 'feather-damaging behaviour' (FDB) that suggests compromised welfare. Susceptibilities to FDB have been suggested, but not empirically demonstrated, to vary across the more than 200 species kept in captivity. Other demographic risk factors have been proposed for particular species - but neither confirmed nor generalised across Psittaciformes. In this preliminary study, we analysed data from a previously-conducted survey of pet owners: among 538 companion parrots representing 10 non-domesticated, non-hybrid species (n≥17/species), FDB prevalence was 15.8% overall. We tested whether individual FDB status was predicted by four previously-suggested demographic risk factors: species, sex, age, or hatch origin. Available (limited) data on husbandry were assessed as potential confounding variables and controlled for as appropriate. Species identity was a predictor of FDB status (P=0.047), even after controlling for all other variables tested; however, in light of multiple statistical testing, this effect cannot be considered robust until it is replicated. The strongest predictors of FDB status were age (P=0.001; with odds of positive FDB status lower in juveniles versus adolescents or adults [P 0.036]), and sex (P 0.006; with odds of FDB lower in individuals of unknown, versus known, sex [P 0.037]). These findings need to be replicated with data that allow better statistical controls for systematic differences in housing. However, they do provide preliminary empirical evidence for within-species risk factors (suggesting new, testable hypotheses about the etiology of parrot FDB); and for intrinsic, cross-species differences in FDB susceptibility (providing a rationale for future study of the biological factors that might underpin any such taxonomic differences)