<p>Mesenchymal Stem Cells Application in Wound Tissue Healing in Old Animals</p>

Abstract

Purpose An assessment of the effectiveness of progenitor mesenchymal stem cell as injections and as part of a polymer hydrogel for the wounds treatment. Materials and Methods Fixed-size wounds (average area of 135.8 mm 2 ) were modeled on the back of white Wistar rats, aged 9 months. Mesenchymal stem cells (MSC) isolated from a human umbilical cord were injected into the wounds once on the modeling day (SC group). In other animals, MSC were periodically applied externally as one of the components in the polymer hydrogel (Polymer_sc group). The systemic effect of the cells was assessed via the analysis of intact contralateral wounds located on the opposite side of the same animal’s back (groups Control_sc and Control_Psc, respectively). The reference intact wounds belonged to the Control_0 group. The wound area was studied in dynamics. Descriptive microscopy was supplemented by an assessment of the collagen fibers’ maturity, the epidermal layers, and the number of fibroblasts and leukocytes in different parts of the wounds. Results Both the local and systemic application of MSC led to an improvement in wound regeneration. During the acute inflammatory phase (up to 3 days), the method and place of application did not affect the dynamics of wound healing. The use of Polymer_sc ultimately demonstrated the best effectiveness. The anti-inflammatory effect of MSC was confirmed by a decrease in leukocyte infiltration in the wound centers (Polymer_sc and SC groups) and edges (all groups, with the greatest extent in the Polymer_sc group). The proliferative phase that expresses itself via accelerated growth in fibroblast number and collagen production was affected in the Control_Psc group and mostly in the Polymer_sc group. Conclusion The applications of MSC in various ways improve and accelerate wound healing even in old animals. The best performance was achieved in the Polymer_sc group.

Application of Polymer Drugs with Cerium Dioxide Nanomolecules and Mesenchymal Stem Cells for the Treatment of Skin Wounds in Aged Rats

“…Thus, the effectiveness of the use of SPN and SPN + SC for the treatment of wounds has been determined. The results obtained are consistent with the opinion of earlier studies on the effective use of polymers [ 10 , 11 , 12 , 13 , 14 , 24 ] and molecules of cerium dioxide [ 20 , 21 , 22 , 23 , 24 , 25 ] for the treatment of wounds. In addition, our study confirms the results of other studies that the introduction of nanoparticles of certain substances radically changes the effectiveness of drugs, and this represents a quantum leap in providing safe and effective targeted drug delivery to the affected tissues [ 31 , 32 ].…”

“…Group of mesenchymal stem cells (SC)—a culture of mesenchymal stem cells at a concentration of 100,000 SC per wound) was injected into the edges of the wounds of this group on the modeling day (0.2 mL: 0.1 mL of SC was injected into the lateral edge, and 0.1 mL of SC into the caudal edge). SC were isolated from the umbilical cord of a newborn after normal delivery at 38–40 weeks of gestation with the informed consent of a healthy mother and produced after the fourth passage by technology [ 25 , 26 ]. After the isolation process, the stem cells had a standard morphological structure of cells grown in a MEM culture medium (Lonsa), StemPro ™ MSC (Gibco, Grand Island, NY, USA), at a concentration of 0.5 × 10 6 per 1 mL.…”

“…As a result, the concentration of substances in the gel base of the matrix was (in mass percent): carboxymethyl cellulose—1.0; pectin—0.1; chitosan—0.01; agar—0.1; alginate—0.05; cerium oxide in the form of a colloidal sol of nanoparticles—0.0002. A preliminary analysis of the developed agent, as well as the results of experiments, demonstrating its safety and biocompatibility, were presented earlier [ 24 , 25 , 29 , 30 ]. SPN was applied topically once a day on day 0, 1, 3, 5, and 7 by applying it over the wound with a needle-free syringe and filling its volume using 1 mL per cm 2 .…”

“…This gives us reason to call such substances smart nano-drugs. Scientists from different countries have demonstrated the effectiveness of using cerium oxide nanoparticles for healing skin wounds [ 20 , 21 , 22 , 23 , 24 , 25 ]. Since the theory of oxidative stress as the main mechanism of cell death and the occurrence or maintenance of non-healing wounds is gaining increasing confirmation, the researchers decided to study the effect of these agents (factors) on the healing of experimental acute wounds in animals.…”

Acute Skin Wounds Treated with Mesenchymal Stem Cells and Biopolymer Compositions Alone and in Combination: Evaluation of Agent Efficacy and Analysis of Healing Mechanisms

“…However, not enough research has yet been done investigating this new direction to provide data that meet all the requirements of evidence-based medicine. In our previous research, we developed new dressing biomaterials for the treatment of wounds containing polymers, mesenchymal stem cells, and nanoparticles of cerium dioxide (CeO2), and demonstrated their preliminary safety and efficacy [30][31][32][33][34]. We have chosen CeO2 nanoparticles as the metal included in our biomaterials because previous studies have shown that it has low toxicity and high biocompatibility, as well as the ability, depending on the changing pH of the wound, to provide electron transfer through the transition from Ce3+ to Ce4+ valence and vice versa [35][36][37][38].…”