Abstract
Pluripotent stem cells (PSCs) hold, through the capacity to differentiate into virtually all body cell types, unprecedented promise for human and animal medicine. PSCs are naturally found in the early embryo, and in rodents and humans they can be robustly harvested and grown in culture in the form of embryonic stem cells (ESCs); however, the availability of ESCs from horses is limited. ES-like cells named induced pluripotent stem cells (iPSCs) can be derived in vitro by transcription factor-mediated reprogramming of adult cells. As such, iPSCs can be generated in a patient-specific manner providing unmatched potential for tissue transplantation and in vitro disease modeling. In humans, clinical trials using iPSC-derived cells are already taking place and the use of in vitro iPSC models has identified novel mechanisms of disease and therapeutic targets. Although to a more limited extent, iPSCs have also been generated from horses, a species in which, after humans, these cells are likely to hold the greatest potential in regenerative medicine. Before a clinical use can be envisioned, however, significant challenges will need to be addressed in relation to the robust derivation, long-term culture, differentiation, and clinical safety of equine iPSCs. Toward this objective, recent studies have reported significant improvement in culture conditions and the successful derivation for the first time of functional cell types from equine iPSCs. Given the wide range of exciting applications they could have, it is hoped future research will make the biomedical promise of iPSCs a reality not only for humans but also horses.
Highlights
Pluripotent stem cells (PSCs) hold, through the capacity to differentiate into virtually all body cell types, unprecedented promise for human and animal medicine
Stem cells are defined based on their capacity for self-renewal and the ability to differentiate into specialized cell types
In contrast to multipotent stem cells, pluripotent stem cells (PSCs) are intrinsically able to self-renew indefinitely and to give rise to virtually all cell types in the body, features that provide distinct advantages in relation to regenerative medicine applications and for which PSCs have been the subject of intense research over the past 30 years
Summary
To a more limited extent, iPSCs have been generated from horses, a species in which, after humans, these cells are likely to hold the greatest potential in regenerative medicine. ESC lines that maintain their pluripotency in vivo, i.e., are able to give raise to differentiated teratomas when injected into immunodeficient mice, have been robustly derived from rodents and humans but not, to this date, from domestic species, including the horse. This is partly attributed to the relative lack of knowledge of early embryo development in domestic species, which precludes the use of optimal conditions to stably maintain embryonic cells in an undifferentiated state. Cultures of equine embryonic cells that lack pluripotency in vivo have been established by several groups [3, 4] and their potential in relation to veterinary regenerative medicine is being investigated [5, 6]
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