Macroscopic, Histologic, and Immunomodulatory Response of Limb Wounds Following Intravenous Allogeneic Cord Blood-Derived Multipotent Mesenchymal Stromal Cell Therapy in Horses

Abstract

Limb wounds are common in horses and often develop complications. Intravenous multipotent mesenchymal stromal cell (MSC) therapy is promising but has risks associated with intravenous administration and unknown potential to improve cutaneous wound healing. The objectives were to determine the clinical safety of administering large numbers of allogeneic cord blood-derived MSCs intravenously, and if therapy causes clinically adverse reactions, accelerates wound closure, improves histologic healing, and alters mRNA expression of common wound cytokines. Wounds were created on the metacarpus of 12 horses. Treatment horses were administered 1.51–2.46 × 108 cells suspended in 50% HypoThermosol FRS, and control horses were administered 50% HypoThermosol FRS alone. Epithelialization, contraction, and wound closure rates were determined using planimetric analysis. Wounds were biopsied and evaluated for histologic healing characteristics and cytokine mRNA expression. Days until wound closure was also determined. The results indicate that 3/6 of treatment horses and 1/6 of control horses experienced minor transient reactions. Treatment did not accelerate wound closure or improve histologic healing. Treatment decreased wound size and decreased all measured cytokines except transforming growth factor-β3. MSC intravenous therapy has the potential to decrease limb wound size; however, further work is needed to understand the clinical relevance of adverse reactions.

Recent Progress on Hyaluronan-Based Products for Wound Healing Applications

“…Skin lacerations caused by physical, chemical, and thermal factors initiate the wound healing process. However, wounds may become chronic as a result of loss of fluids, excessive inflammation, and other hurdles that prevent or delay wound healing [ 12 , 13 , 14 ]. To circumvent these limitations of the wound healing process, tissue engineers have developed various biomaterials, such as hydrogels, membranes, fibers, and nanocomposites.…”

The use of RNA-based treatments in the field of cancer immunotherapy

“…TriMix mRNA was proven to be more immunogenic than unmodified, unpurified mRNA in several cancer vaccination tests, and this effect was most clearly associated to improved DC maturation and cytotoxic T lymphocyte (CTL) responses [112]. It has been proven that the kind of mRNA carrier utilized and the size of the mRNAcarrier complex both have an effect on the cytokine profile that is produced as a result of the injection of mRNA [113]. For example, the carrier is what provides the adjuvant effect for the RNActive (CureVac AG) immunization platform [113].…”

“…It has been proven that the kind of mRNA carrier utilized and the size of the mRNAcarrier complex both have an effect on the cytokine profile that is produced as a result of the injection of mRNA [113]. For example, the carrier is what provides the adjuvant effect for the RNActive (CureVac AG) immunization platform [113]. RNA complexed with protamine, which is a polycationic peptide, works as an adjuvant by increasing TLR7 signaling and is utilized to make the antigen [114].…”