Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

Abstract

This paper provides a bird's-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine.The understanding of equine stem cell biology, biofactors, and scaffolds, and their potential therapeutic use in horses are rudimentary at present. Mesenchymal stem cell isolation has been proclaimed from several equine tissues in the past few years. Based on the criteria of the International Society for Cellular Therapy, most of these cells are more correctly referred to as multipotent mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering - cells, biological factors, and biomaterials - are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources.The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently in controlled clinical trials in equine patients to be regarded as evidence-based medicine. In the meantime, the medical mantra "do no harm" should prevail, and the application of stem cell-based therapies in the horse should be done critically and cautiously, and treatment outcomes (good and bad) should be recorded and reported.Stem cell and tissue engineering research in the horse has exciting comparative and equine specific perspectives that most likely will benefit the health of horses and humans. Controlled, well-designed studies are needed to move this new equine research field forward.

Figure 1

The components of tissue engineering are cells, biological factors, and scaffolds as illustrated by the brown, yellow, and blue circles, respectively. These components can be used alone or in any possible combination. Determination of their mechanism of action and regulatory approval generally becomes increasingly complex and difficult with the number of components included. Figure by Koch and Berg.

Figure 2

Ideally, any scaffold is degraded at a rate optimum for allowing complete tissue regeneration and ultimately replaced entirely by the regenerated tissue. Survival of the transplanted cells and successful tissue integration relies on diffusion of biological factors through the scaffold. The scaffold-tissue transition phase might be associated with decreased mechanical strength and function, leading to treatment failure if the scaffold degrades faster than the tissue can regenerate. On the other hand, a slowly degrading scaffold might impair and, potentially, prevent proper tissue healing. These concepts should be considered when evaluating scaffold-based studies and the time point chosen for evaluation of treatment success. Figure by Koch and Berg.

Figure 3

Autologous osteochondral grafts are currently used in mosaic arthroplasty for selected focal cartilage defects in the horse. Incongruency between graft and native cartilage, as well as reduced biomechanical properties of the graft compared with native cartilage and bone, are the main limitations of the technique today. In the future, tissue engineering and stem cell-based therapies may help to negate these limitations. The asterisk (*) marks 1 of several autologous osteochondral grafts placed in the medial femoral condyle following harvest from the medial trochlear ridge of the same stifle joint. Image: Courtesy of Dr. Mark Hurtig, University of Guelph.