Reproducibility and Comparative aspects of Terrestrial Housing Systems and Husbandry Procedures in Animal Research Facilities on Study Data.

As mentioned in other chapters, reproducibility of research data is very complicated and has numerous contributors for concerns. This chapter will discuss the animal housing systems and corresponding husbandry practices in regard to current practices and known and potential confounders in the research environment. This area has a very high impact for reproducibility and comparability of study data outcomes.

Position Statement: "Functionally Appropriate Nonhuman Primate Environments" as an Alternative to the Term "Ethologically Appropriate Environments".

The American Society of Primatologists (ASP), the Association of Primate Veterinarians (APV), and the American College of Laboratory Animal Medicine (ACLAM) have come together to develop this position statement in which the term "functionally appropriate nonhuman primate environments" is proposed as a better descriptor and as an alternative to the previously used term, "ethologically appropriate environments" to describe environments that are suitable for nonhuman primates involved in biomedical research. In 2015, the United States Department of Agriculture requested comments on a petition which called for amending the Animal Welfare Act so that all research primates would be housed in "ethologically appropriate physical and social environments." We are critical of this term because: (1) it does not provide clarification beyond that in current regulatory language; (2) it does not provide for balance between animal welfare goals and the reasons why the primates are housed in captivity; (3) it discounts the adaptability that is inherent in the behavior of primates; (4) it conveys that duplication of features of the natural environment are required for suitable holding environments; (5) objective studies reveal that environments that appear to be more ethologically appropriate do not necessarily better meet the needs of animals; and (6) using the term "ethology" is inherently confusing. We propose that the term "functionally appropriate nonhuman primate environments" be used instead, as it emphasizes how environments work for nonhuman primates, it better describes current activities underway to improve nonhuman primate welfare, and the balance that is achieved between meeting the needs of the animals and the requirements of the research in which they are involved.

Phenotypic correction of hemophilia A in sheep by postnatal intraperitoneal transplantation of FVIII-expressing MSC.

We recently re-established a line of sheep that accurately mimics the clinical symptoms and genetics of severe hemophilia A (HA). Here, we tested a novel, nonablative transplantation therapy in two pediatric HA animals. Paternal mesenchymal stem cells (MSC) were transduced with a porcine FVIII-encoding lentivector and transplanted via the intraperitoneal route without preconditioning. At the time of transplantation, these animals had received multiple human FVIII treatments for various spontaneous bleeds and had developed debilitating hemarthroses, which produced severe defects in posture and gait. Transplantation of transduced MSC resolved all existent hemarthroses, and spontaneous bleeds ceased. Damaged joints recovered fully; the animals regained normal posture and gait and resumed normal activity. Despite achieving factor-independence, a sharp rise in pre-existent Bethesda titers occurred following transplantation, decreasing the effectiveness and duration of therapy. Postmortem examination revealed widespread engraftment, with MSC present within the lung, liver, intestine, and thymus, but particularly within joints affected at the time of transplantation, suggesting MSC homed to sites of ongoing injury/inflammation to release FVIII, explaining the dramatic improvement in hemarthrotic joints. In summary, this novel, nonablative MSC transplantation was straightforward, safe, and converted life-threatening, debilitating HA to a moderate phenotype in a large animal model.