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.

Mesenchymal Stromal cells (MSCs) have a potential role in cell-based therapies. Foetal bovine serum (FBS) is used to supplement the basal cell culture medium but presents several disadvantages and risks. Other alternatives have been studied, including human umbilical cord blood plasma (hUCBP), aiming at the development of xeno-free culturing protocols. A comparative characterization of multicomponent metabolic composition of hUCBP and commercial FBS based on Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate statistical analysis was performed. The analysis of 1H-NMR spectra revealed both similarities and differences between the two proposed supplements. Similar metabolites (amino acids, glucose, lipids and nucleotides) were found in the hUCBP and FBS NMR spectra. The results show that the major difference between the metabolic profiles of the two proposed supplements are due to the significantly higher levels of glucose and lower levels of lactate, glutamate, alanine and branched chain amino acids in hUCBP. Similar or slightly different levels of important proteinogenic amino acids, as well as of nucleotides, lipids were found in the hUCBP and FBS. In order to validate it’s suitability for cell culture, umbilical cord-MSCs (UC-MSCs) and dental pulp stem cells (DPSCs) were expanded using hUCBP. In both hMSCs, in vitro culture with hUCBP supplementation presented similar to improved metabolic performances when compared to FBS. The two cell types tested expressed different optimum hUCBP percentage content. For DPSCs, the optimum hUCBP content was 6% and for UC-MSCs, 4%. Cultured hMSCs displayed no changes in senescence indicators, as well as maintained characteristic surface marker’s expression. FBS substitution was associated with an increase in early apoptosis events, in a dose dependent manner, as well as to slight up- and down-regulation of targeted gene’s expression. Tri-lineage differentiation capacity was also influenced by the substitution of FBS by hUCBP.

The nasal cavity performs several crucial functions in mammals, including rodents, being involved in respiration, behavior, reproduction, and olfaction. Its anatomical structure is complex and divided into several regions, including the olfactory recess where the olfactory mucosa (OM) is located and where the capture and interaction with the environmental odorants occurs. Among the cells of this region are the OM mesenchymal stem cells (MSCs), whose location raises the possibility that these cells could be involved in the peculiar ability of the olfactory nerve to regenerate continuously throughout life, although this relationship has not yet been confirmed. These cells, like all MSCs, present functional characteristics that make them candidates in new therapies associated with regenerative medicine, namely to promote the regeneration of the peripheral nerve after injury. The availability of stem cells to be therapeutically applied essentially depends on their collection in the tissue of origin. In the case of mice and rat's OM-MSCs, knowledge about the anatomy and histology of their nasal cavity is essential in establishing effective collection protocols. The present article describes the morphological characteristics of rodent's OM and establishes an alternative protocol for access to the olfactory recess and collection of the OM. Anat Rec, 301:1678-1689, 2018. © 2018 Wiley Periodicals, Inc.

In 2019, an outbreak of an unknown coronavirus-SARS-CoV-2-responsible for COVID-19 disease, was first reported in China, and evolved into a pandemic of huge dimensions and raised serious concerns for global health. The number of critical cases continues to increase dramatically, while vaccines and specific treatments are not yet available. There are several strategies currently being studied for the treatment of adverse symptoms of COVID-19, that encompass Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS), extensive pulmonary inflammation, cytokine storm, and pulmonary edema, due to virus-induced pneumonia. Mesenchymal stem cells (MSCs) are at the origin of new revolutionary treatments, which may come to be applied in such as Regenerative Medicine, Immunotherapy, Tissue Engineering, and Cell and Molecular Biology due to immunomodulation and anti-inflammatory activity. MSCs have already been studied with positive outcomes for other lung pathologies, thus representing and being identified as an important opportunity for the treatment of COVID-19. It has recently been shown that these cells allow hopeful and effective therapies for serious or critical COVID-19, minimizing its adverse symptoms. In this study we will analyze the MSCs, their origin, differentiation, and therapeutic potential, making a bridge with the COVID-19 disease and its characteristics, as a potential therapeutic strategy but also reporting recent studies where these cell-based therapies were used for the treatment of COVID-19 patients.

Mesenchymal Stem/ Stromal Cells assume a supporting role to the intrinsic mechanisms of tissue regeneration, a feature mostly assigned to the contents of their secretome. A comparative study on the metabolomic and bioactive molecules/factors content of the secretome of Mesenchymal Stem/ Stromal Cells derived from two expanding sources: the umbilical cord stroma and the dental pulp is presented and discussed. The metabolic profile (Nuclear Magnetic Resonance Spectroscopy) evidenced some differences in the metabolite dynamics through the conditioning period, particularly on the glucose metabolism. Despite, overall similar profiles are suggested. More prominent differences are highlighted for the bioactive factors (Multiplexing Laser Bear Analysis), in which Follistatin, Growth Regulates Protein, Hepatocyte Growth Factor, Interleukin-8 and Monocyte Chemotactic Protein-1 dominate in Umbilical Cord Mesenchymal Stem/ Stromal Cells secretion, while in Dental Pulp Stem/ Stromal Cells the Vascular Endothelial Growth Factor-A and Follistatin are more evident. The distinct secretory cocktail did not result in significantly different effects on endothelial cell populations dynamics including proliferation, migration, tube formation capacity and in vivo angiogenesis, or in chemotaxis for both Mesenchymal Stem/ Stromal Cells populations.

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.

Nerve tube-guides based on dextran and poly(ε-caprolactone) were successfully used in the recovery of a neurotmesis injury in rat model.