An animal’s capacity to suffer is a prerequisite for any animal welfare concern, and the minimization of suffering is a key aim of refinement research. In contrast to the traditional focus on avoiding or reducing negative welfare states, modern animal welfare concepts highlight the importance of promoting positive welfare states in laboratory animals. Reliable assessments of affective states, as well as the knowledge of how to elicit positive affective states, are central to this concept. Important achievements have been made to assess pain and other negative affective states in animals in the last decades, but it is only recently that the neurobiology of positive emotions in humans and animals has been gaining more interest. Thereby, the need for promotion of positive affective states for laboratory animals is gaining more acceptance, and methods allowing the assessment of affective states in animals have been increasingly introduced. In this overview article, we present common and emerging methods to assess affective states in laboratory rodents. We focus on the implementation of these methods into applied refinement research to identify achieved progress as well as the future potential of these tools to improve animal welfare in animal-based research.

Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal stem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo. Immunodeficient mice received subcutaneous grafts containing human ECFCs alone, or pairs of human ECFCs/MSCs from the same umbilical cord (UC) to study vasculogenesis in the presence of human leukocyte antigen (HLA)-mismatched human peripheral blood mononuclear cells (PBMCs). In vitro, cell surface marker changes due to interferon gamma (IFNγ) stimulation during ECFC/MSC coculture were determined and further effects on allostimulated T cell proliferation and cytotoxic lysis were measured. IFNγ-induced HLA-DR expression on ECFCs and MSCs, but both cell types had significantly less HLA-DR in cocultures. ECFC-induced T cell proliferation was abolished after MSC coculture as a result of HLA-DR downregulation and indolamin-2,3-dioxygenase activation. Additionally, allospecific CD8 T cell-mediated lysis of ECFCs was reduced in cocultures. ECFC/MSC coapplication in immunodeficient mice not only promoted the generation of improved blood vessel architecture after 6 weeks, but also reduced intragraft immune cell infiltration and endothelial HLA-DR expression following PBMC reconstitution. Crosstalk between UC-derived ECFCs and MSCs after combined transplantation can lower the risk of ECFC rejection, thus enabling their coapplication for therapeutic vasculogenesis. Stem Cells 2017;35:1233-1245.

Supplemental material:Figure S1: Slightly increasing body weight during habituation period Body weight [g] at day one and six of habituation period per strain were presented as box plot with median and whiskers [2.5, 97.5 %] (n = 38 C57BL/6J: p-value = 0.0018, n = 15 BALB/cJ: p-value = 0.0004 and n = 15 129S1/SvImJ: p-value < 0.0001, Wilcoxon matchedpairs signed rank test, two-tailed).

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From the preference of one good over another, the strength of the preference cannot automatically be inferred. While money is the common denominator to assess the value of goods in humans, it appears difficult at first glance to put a price tag on the decisions of laboratory animals. Here we used consumer demand tests to measure how much work female mice expend to obtain access to different liquids. The mice could each choose between two liquids, one of which was free. The amount of work required to access the other liquid, by contrast, increased daily. In this way, the value of the liquid can be determined from a mouse's microeconomic perspective. The unique feature is that our test was carried out in a home-cage based setup. The mice lived in a group but could individually access the test-cage, which was connected to the home-cage via a gate. Thereby the mice were able to perform their task undisturbed by group members and on a self-chosen schedule with minimal influence by the experimenter. Our results show that the maximum number of nosepokes depends on the liquids presented. Mice worked incredibly hard for access to water while a bitter-tasting solution was offered for free whereas they made less nosepokes for sweetened liquids while water was offered for free. The results demonstrate that it is possible to perform automated and home-cage based consumer demand tests in order to ask the mice not only what they like best but also how strong their preference is.