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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., Competing Interests: The authors have declared that no competing interests exist.

The healing process of the skin is a dynamic procedure mediated through a complex feedback of growth factors secreted by a variety of cells types. Despite the most recent advances in wound healing management and surgical procedures, these techniques still fail up to 50%, so cellular therapies involving mesenchymal stem cells (MSCs) are nowadays a promising treatment of skin ulcers which are a cause of high morbidity. The MSCs modulate the inflammatory local response and induce cell replacing, by a paracrine mode of action, being an important cell therapy for the impaired wound healing. The local application of human MSCs (hMSCs) isolated from the umbilical cord Wharton's jelly together with a poly(vinyl alcohol) hydrogel (PVA) membrane, was tested to promote wound healing in two dogs that were referred for clinical examination at UPVET Hospital, showing non-healing large skin lesions by the standard treatments. The wounds were infiltrated with 1000 cells/µl hMSCs in a total volume of 100 µl per cm(2) of lesion area. A PVA membrane was applied to completely cover the wound to prevent its dehydration. Both animals after the treatment demonstrated a significant progress in skin regeneration with decreased extent of ulcerated areas confirmed by histological analysis. The use of Wharton's jelly MSCs associated with a PVA membrane showed promising clinical results for future application in the treatment of chronic wounds in companion animals and humans.

Simple Summary: Musculoskeletal injuries in sport horses are relatively common and quite worrisome. Tendon and ligament injuries in sport horses usually result in a long period of time out of competition. Their healing usually results in tissue fibrosis and concomitant loss of elasticity, which, depending on the severity, might prevent the horse's recovery to the same performance levels or even to athletic levels. The continuous development of regenerative medicine offers therapeutical promise. Synovial membrane mesenchymal stem/stromal cells (SM-MSCs) and umbilical cord mesenchymal stem/stromal cells (UC-MSC), as well as their growth factors, have been described as having optimal characteristics for tendon and ligament regeneration. Therefore, a therapeutical combination of SM-MSC and a conditioned medium of UC-MSC was developed, produced, and administered on a tarsal long medial collateral ligament desmitis of a show-jumping horse. The production and application of the orthobiologic therapeutical combination as well as the clinical outcome are presented herein. Horses are high-performance athletes prone to sportive injuries such as tendonitis and desmitis. The formation of fibrous tissue in tendon repair remains a challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance regeneration, retrieving original tissue properties. Multipotent Mesenchymal Stem/Stromal Cells (MSCs) have been successfully used to develop therapeutic products, as they secrete a variety of bioactive molecules that play a pivotal role in tissue regeneration. These factors are released in culture media for producing a conditioned medium (CM). The aforementioned assumptions led to the formulation of equine synovial membrane MSCs (eSM-MSCs)—the cellular pool that naturally regenerates joint tissue—combined with a medium enriched in immunomodulatory factors (among other bioactive factors) produced by umbilical cord stroma-derived MSCs (eUC-MSCs) that naturally contribute to suppressing the immune rejection in the maternal–fetal barrier. A description of an equine sport horse diagnosed with acute tarsocrural desmitis and treated with this formulation is presented. Ultrasonographic ligament recovery occurred in a reduced time frame, reducing stoppage time and allowing for the horse's return to unrestricted competition after the completion of a physical rehabilitation program. This study focused on the description of the therapeutic formulation and potential in an equine desmitis treatment using the cells themselves and their secretomes. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells are posing as a promising character in the most recent therapeutic strategies and, since their discovery, extensive knowledge on their features and functions has been gained. In recent years, innovative sources have been disclosed in alternative to the bone marrow, conveying their associated ethical concerns and ease of harvest, such as the umbilical cord tissue and the dental pulp. These are also amenable of cryopreservation and thawing for desired purposes, in benefit of the donor itself or other patients in pressing need. These sources present promising possibilities in becoming useful cell sources for therapeutic applications in the forthcoming years. Effective and potential applications of these cellular-based strategies for the regeneration of peripheral nerve are overviewed, documenting recent advances and identified issues for this research area in the near future. Finally, besides the differentiation capacities attributed to mesenchymal stem cells, advances in the recognition of their effective mode of action in the regenerative theatre have led to a new area of interest: the mesenchymal stem cells’ secretome. The paracrine modulatory pathway appears to be a major mechanism by which these are beneficial to nerve regeneration and comprehension on the specific growth factors, cytokine, and extracellular molecules secretion profiles is therefore of great interest. [ABSTRACT FROM AUTHOR]

Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. Neonatal tissues are routinely discarded at parturition so little ethical controversy attends the harvest of the Mesenchymal Stem Cells (MSCs) which may play an important therapeutic role through the secretion of soluble trophic factors which enhance and assist in repair by paracrine activation of surrounding cells. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in our recent research work we have been evaluating the therapeutic value of MSCs isolated from the Wharton jelly (WJ) in nerve repair associated to different tube-guides made of biodegradable and biocompatible biomaterials. The WJ MSCs in vitro studies included cell characterization by immunocytochemistry, karyotype analysis, tri-lineage differentiation capacity and flow cytometry and also citocompatibility by measuring the intracellular calcium concentration ([Ca 2+ ] i ) in the presence of different tube-guides. Biomaterials like PVA, PVA loaded with MWCNTs (functionalized carbon nanotubes, PVA-CNTs), PVA loaded with polypyrrole (PVA-PPy), and PLC associated to MSCs were tested in terms of cytocompatibility and in vivo in the rat sciatic nerve neurotmesis injury model. The regenerated nerves and tibialis anterior (TA) muscles were processed for stereological studies after 20 weeks. The functional recovery was assessed serially for gait biomechanical analysis, by EPT, SFI and SSI, and by WRL. Histopathology of lung, liver, kidneys, regional lymph nodes ensured the biomaterials biocompatibility. The karyotype analysis of the MSCs excluded the presence of neoplastic signs, thus supporting the suitability of isolation and expansion protocols. The MSCs were positive for C-kit, Nanog and vimentin, and negative for CD31, following the International Society for Cellular Therapy (ISCT) definition. Results obtained from epifluorescence by measuring the [Ca 2+ ] i of the MSCs cultured on tube-guides confirmed the ability to support their expansion, adhesion, and differentiation. Our results showed that the use of MSCs enhanced the recovery of sensory and motor function in neurotmesis injuries showing a thicker myelin sheath. MSCs isolated from WJ delivered through biomaterials should be regarded as a potentially valuable tool to improve clinical outcome especially after trauma to sensory nerves. In addition, these cells represent a non controversial source of primitive mesenchymal progenitor cells that can be harvested after birth, cryogenically stored, thawed, and expanded for therapeutic uses. [ABSTRACT FROM AUTHOR]