Translating stem cell therapies: the role of companion animals in regenerative medicine

Abstract

Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell research in veterinary medicine has facilitated the development and in some instances clinical translation of a variety of cell-based therapies involving hematopoietic stem cells and mesenchymal stem cells, as well as other adult regenerative cells and recently embryonic stem cells and induced pluripotent stem cells. In fact, many of the pioneering developments in these fields of stem cell research have been achieved through collaborations of veterinary and human scientists. This review aims to provide an overview of the contribution of large animal veterinary models in advancing stem cell therapies for both human and clinical veterinary applications. Moreover, in the context of the "One Health Initiative," the role veterinary patients may play in the future evolution of stem cell therapies for both human and animal patients will be explored.

Figure 1. Schematic illustration of strategies for optimization of cell-based therapies in veterinary regenerative medicine

Optimization of stem cell therapies to maximize therapeutic potential may involve identification of superior donor cell populations and characteristics, pre-delivery cell expansion/differentiation protocols, and methods for delivery. Clinical trials involving companion animals as large animal translational models will provide important contributions in identifying under what circumstances allogenic or autologous MSC-based therapies are preferred as well as the optimal site from which to harvest these cells. Elucidation of pre-delivery strategies which improve isolation and enrichment of cells or “prime” desired responses of delivered cells through in vitro manipulation with extracellular matrix components (ECM), growth factors or genetic manipulation may further enhance therapeutic efficacy. Finally, the full potential of cell based therapies can only be realized with identification of appropriate recipient populations, optimal timing and route of delivery, as well as biomaterials that may enhance proregenerative activities of delivered stem cells.