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



Pourmohammadibejarpasi Z1 ; Sabzevari R1 ; Roushandeh AM2, 3 ; Ebrahimi A1 ; Mobayen M3 ; Jahaniannajafabadi A4 ; Darjani A5 ; Roudkenar MH2, 3
Authors
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Authors Affiliations
  1. 1. Medical Biotechnology Department, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
  2. 2. Cellular and Molecular Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
  3. 3. Burn and Regenerative Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
  4. 4. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Skin Research Center, Department of Dermatology, Razi Hospital, School of Medicine, Guilan University of Medical Science, Rasht, Iran

Source: Advanced Pharmaceutical Bulletin Published:2022


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 2 (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 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, MetadicholMSCs 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. © 2022 Tabriz University of Medical Sciences. All rights reserved.
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