Combination Therapy of Metadichol Nanogel and Lipocalin-2 Engineered Mesenchymal Stem Cells Improve Wound Healing in Rat Model of Excision Injury
Zahra Pourmohammadi-Bejarpasi
1 
, Reza Sabzevari
1, Amaneh Mohammadi Roushandeh
2,3, Ammar Ebrahimi
1, Mohammadreza Mobayen
3, Ali Jahanian-Najafabadi
4, Abbas Darjani
5* , Mehryar Habibi Roudkenar
2,3* 1 Medical Biotechnology Department, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht, Iran.
2 Cellular and Molecular Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran.
3 Burn and Regenerative Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran.
4 Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
5 Skin Research Center, Department of Dermatology, Razi Hospital, School of Medicine, Guilan University of Medical Science, Rasht, Iran.
*Corresponding Authors: Abbas Darjani and Mehryar Habibi Roudkenar, Email; darjani@gums.ac.ir and Email; roudkenar@gums.ac.ir, Email:
-; Abbas Darjani and Mehryar Habibi Roudkenar, Email; darjani@gums.ac.ir and Email; roudkenar@gums.ac.ir, Email:
mhr376@yahoo.com
Abstract
Purpose: Currently, several disorders including burns, trauma, excisional and diabetic wounds,and bedsores threaten the human health. Application of mesenchymal stem cells (MSCs) isrecommended for treatment of skin disorders. However, because of oxidative stress andinflammation after skin injury, survival of transplanted MSCs is low which in turn negativelyaffects the efficiency of the MSCs-based therapy. In an attempt to address the aforementionedchallenge and introducing a novel potential therapeutic strategy, we employed combinationtherapy by lipocalin 2 (Lcn2)-engineered MSCs and a Metadichol (an inverse agonist of vitaminD receptor (VDR)) nanogel in a rat model of excisional wound.Methods: First, human umbilical cord MSCs (hUC-MSCs) was transfected by a recombinantplasmid encoding Lcn2 gene. Next, a combination of Metadichol nanogel and the engineeredMSCs was co-applied on wound in rat model of excision injury. Finally the improvementof wound healing in experimental groups was evaluated by photography and histologicalassessments (hematoxylin and eosin staining).Results: Our findings revealed that the repair rate was higher in the group received combinationtherapy comparing to control groups. Notably, Metadichol+Lcn2-MSCs showed significantlyhigher 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 inthe treatment groups. Our results also revealed that the combination therapy improved andaccelerated the wound healing process.Conclusion: Our findings suggest a novel potential therapeutic strategy i.e. Lcn2-engineeredMSCs and Metadichol for wound healing. However, further preclinical and clinical studies arerequired.