Combination Therapy of Metadichol Nanogel and Lipocalin-2 Engineered Mesenchymal Stem Cells Improve Wound Healing in Rat Model of Excision Injury

Abstract

Purpose: Currently, several disorders including burns, trauma, excisional and diabetic wounds, and bedsores threaten the human health. Application of mesenchymal stem cells (MSCs) is recommended for treatment of skin disorders. However, because of oxidative stress and inflammation after skin injury, survival of transplanted MSCs is low which in turn negatively affects the efficiency of the MSCs-based therapy. In an attempt to address the aforementioned challenge and introducing a novel potential therapeutic strategy, we employed combination therapy by Lipocalin (Lcn2)-engineered MSCs and a Metadichol (an inverse agonist of vitamin D receptor (VDR)) nanogel in a rat model of excisional wound. Methods: First, Human umbilical cord MSCs (hUC-MSCs) was transfected by a recombinant plasmid encoding Lipocalin 2 (Lcn2) gene. Next, a combination of Metadichol nanogel and the engineered MSCs was co-applied on wound in rat model of excision injury. Finally the improvement of wound healing in experimental groups was evaluated by photography and histological assessments (hematoxylin and eosin staining). Results: Our findings revealed that the repair rate was higher in the group received combination therapy comparing to control groups. Notably, Metadichol+Lcn2-MSCs showed significantly higher wound contraction rate compared to control group at all time points (p value< 0.001). Furthermore, wound repair rate was 95% 14 days after surgery, and 100% after 21 days in the treatment groups. Our results also revealed that the combination therapy improved and accelerated the wound healing process. Conclusion: Our findings suggest a novel potential therapeutic strategy i.e. Lcn2-engineered MSCs and Metadichol for wound healing. However, further preclinical and clinical studies are required.

Polyacrylic acid/ polyvinylpyrrolidone hydrogel wound dressing containing zinc oxide nanoparticles promote wound healing in a rat model of excision injury

“…Excisional wound was developed according to Pourmohammadi-Bejarpasi et al study [ 34 ]. Briefly, anesthesia was administrated by intraperitoneal injection (Ketamine (70 mg/kg) and Xylazine (7 mg/kg)).…”

Mesenchymal Stromal Cell Healing Outcomes in Clinical and Pre-Clinical Models to Treat Pressure Ulcers: A Systematic Review

“…The disparity in healing rates can be attributable to different mechanisms of action and the nature of the therapies used. While ADSCs directly impact crucial early-stage healing processes, the combination therapy in the Pourmohammadi et al [22] study might have had a more gradual yet effective healing impact. These observations underscore the potential of MSCs in wound healing, especially for pressure ulcers, and highlight the importance of considering the type of MSCs and the therapeutic approach in designing treatment strategies.…”

“…Pourmohammadi-Bejarpasi, Z. et al [22] investigated the use of lipocalin 2 (Lcn2)engineered MSCs and Metadichol (an inverse agonist of vitamin D receptor (VDR)) nano gel for the treatment of skin disorders such as burns, trauma, excisional and diabetic wounds, and bedsores in 2022. The effectiveness of the combination therapy was evaluated using an excisional wound rat model.…”

“…nhADSCs showed improved regenerative ability, significantly impacting critical healing processes such as inflammation reduction, angiogenesis, and collagen deposition, resulting in wound closure by day 17. Pourmohammadi et al's trial [22], which used a combination therapy of Lcn2-engineered MSCs and Metadichol, achieved a 95% repair rate by day 14 and complete healing by day 21. The disparity in healing rates can be attributable to different mechanisms of action and the nature of the therapies used.…”

Nanogels for bone tissue engineering – from synthesis to application

“…The combination therapy enhanced wound contraction and gave 100% wound repair after 21 days of surgical intervention. 108 Nanogels are versatile and can change their phase (sol–gel or gel–sol transition) according to temperature. Thus, they have unique applications in terms of less invasive surgery to treat such pathologies.…”