The use of rats and mice as animal models in ex vivo bone growth and development studies

Abstract

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine.Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2.

Ex Vivo Organ Cultures as Models to Study Bone Biology

“…However, it is important to note that the traditional ex vivo bone organ cultures have several disadvantages, such as deficiency of blood supply, culture media perfusion, cell death and cell migration out of the bones after longer periods of culture, as well as the need to use highly rich culture media for applications requiring long‐term culture. Current research efforts are focused on reducing these limitations by incorporating bioreactors that increase tissue perfusion and the development of chorioallantoic membrane culture systems, as discussed in reference . In summary, ex vivo bone organ cultures are a unique and powerful platform for revealing cellular and molecular insights in bone biology, as well as the rapid screening of drugs and therapies.…”

“…Importantly, findings using ex vivo bone organ cultures faithfully reproduce results seen in in vivo animal models. Ex vivo bone organ cultures were originally used for the investigation of the mechanisms underlying bone growth, bone and cartilage matrix turnover, and the effects of cancer in bone . More recently, this system has been employed to study mechanical loading, interactions between different bone cell types, and the molecular steps involved in bone resorption and formation.…”

“…Ex vivo bone organ cultures were originally used for the investigation of the mechanisms underlying bone growth, bone and cartilage matrix turnover, and the effects of cancer in bone. (14)(15)(16)(17)(18)(19)(20) More recently, this system has been employed to study mechanical loading, interactions between different bone cell types, and the molecular steps involved in bone resorption and formation. In this article, we describe the procedures optimized by our group to establish ex vivo whole-bone organ cultures and osteocyte-enriched bone organ cultures ( Fig.…”

Animal experimentation: A look into ethics, welfare and alternative methods

“…These limitations led to the development of a cost-effective ex vivo model that can effectively replace in vivo and in vitro models, thus contributing to animal welfare. 26 Ex vivo models can be used to develop new therapies in which the disease can be identified at an earlier stage and treated with very advanced techniques. In dentistry, with the development of an ex vivo culture model, the investigation of inflammatory cell behavior and metabolism in different types of periodontal disease has become easy.…”

“…In dentistry, with the development of an ex vivo culture model, the investigation of inflammatory cell behavior and metabolism in different types of periodontal disease has become easy. 23,26 investigators' ethics…”