Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

With high clinical interest to be applied in regenerative medicine, Mesenchymal Stem/Stromal Cells have been widely studied due to their multipotency, wide distribution, and relative ease of isolation and expansion in vitro. Their remarkable biological characteristics and high immunomodulatory influence have opened doors to the application of MSCs in many clinical settings. The therapeutic influence of these cells and the interaction with the immune system seems to occur both directly and through a paracrine route, with the production and secretion of soluble factors and extracellular vesicles. The complex mechanisms through which this influence takes place is not fully understood, but several functional manipulation techniques, such as cell engineering, priming, and preconditioning, have been developed. In this review, the knowledge about the immunoregulatory and immunomodulatory capacity of MSCs and their secretion products is revisited, with a special focus on the phenomena of migration and homing, direct cell action and paracrine activity. The techniques for homing improvement, cell modulation and conditioning prior to the application of paracrine factors were also explored. Finally, multiple assays where different approaches were applied with varying success were used as examples to justify their exploration.

Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions, larger than conventional laboratory animals, but very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with a focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research.

Tendon and ligament injuries are frequent in sport horses and humans, and such injuries represent a significant therapeutic challenge. Tissue regeneration and function recovery are the paramount goals of tendon and ligament lesion management. Nowadays, several regenerative treatments are being developed, based on the use of stem cell and stem cell-based therapies. In the present study, the preparation of equine synovial membrane mesenchymal stem cells (eSM-MSCs) is described for clinical use, collection, transport, isolation, differentiation, characterization, and application. These cells are fibroblast-like and grow in clusters. They retain osteogenic, chondrogenic, and adipogenic differentiation potential. We present 16 clinical cases of tendonitis and desmitis, treated with allogenic eSM-MSCs and autologous serum, and we also include their evaluation, treatment, and follow-up. The concerns associated with the use of autologous serum as a vehicle are related to a reduced immunogenic response after the administration of this therapeutic combination, as well as the pro-regenerative effects from the growth factors and immunoglobulins that are part of its constitution. Most of the cases (14/16) healed in 30 days and presented good outcomes. Treatment of tendon and ligament lesions with a mixture of eSM-MSCs and autologous serum appears to be a promising clinical option for this category of lesions in equine patients.

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk-aggravating factors for the development of chronic skin lesions. Stem cells’ regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of three-dimensional (3D) bioprinted scaffolds. With this review, we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, in terms of their relevance in the skin regeneration field.