Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2020; 12(12): 1652-1666
Published online Dec 26, 2020. doi: 10.4252/wjsc.v12.i12.1652
Umbilical cord-derived mesenchymal stem cells preconditioned with isorhamnetin: potential therapy for burn wounds
Shazmeen Aslam, Irfan Khan, Fatima Jameel, Midhat Batool Zaidi, Asmat Salim
Shazmeen Aslam, Irfan Khan, Fatima Jameel, Midhat Batool Zaidi, Asmat Salim, Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 74700, Sindh, Pakistan
Author contributions: Aslam S performed all experiments, analyzed the data and wrote the first draft of the manuscript; Khan I and Salim A conceived the idea, designed the experiments, and assisted in data analysis; Salim A wrote the final manuscript; Jameel F assisted in the in vivo models and wrote part of the manuscript; Zaidi MB assisted in the in vitro studies and image analysis; all authors approved the final version of the article.
Institutional review board statement: The study was reviewed and approved by the Independent Ethics Committee of International Center for Chemical and Biological Sciences, University of Karachi (ICCBS/IEC-036-HT-2018/Protocol/1.0).
Institutional animal care and use committee statement: The study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the International Center for Chemical and Biological Sciences, University of Karachi (Animal study protocol number: 2018-0018).
Conflict-of-interest statement: The authors have nothing to disclose.
Data sharing statement: Informed consent regarding the experiments in the current study was received from all participants. No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Asmat Salim, PhD, Professor, Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, University Road, Karachi 74700, Sindh, Pakistan. asmat.salim@iccs.edu
Received: July 30, 2020
Peer-review started: July 30, 2020
First decision: September 17, 2020
Revised: October 1, 2020
Accepted: October 26, 2020
Article in press: October 26, 2020
Published online: December 26, 2020
Processing time: 149 Days and 18.5 Hours
ARTICLE HIGHLIGHTS
Research background

Impaired wound healing can be associated with different pathological states. Burn wounds are the most common and detrimental injuries that remain a major health issue worldwide. Mesenchymal stem cells (MSCs) possess the ability to regenerate tissues by secreting factors involved in promoting cell migration, proliferation and differentiation, while suppressing immune reactions. Preconditioning of MSCs with small molecules having cytoprotective properties can enhance the potential of these cells for their use in cell-based therapeutics.

Research motivation

Mesenchymal stem cells are a promising source for cell-based treatment to achieve skin regeneration. Preconditioning approaches using treatment with cytoprotective agents can lead to improvement in the wound healing potential of these stem cells and would be a crucial step in defining efficient therapy following burn injuries.

Research objectives

The objective of this study was to enhance the therapeutic potential of human umbilical cord MSCs (hU-MSCs) by preconditioning them with the cytoprotective flavonoid compound, isorhamnetin in a second degree burn wound model.

Research methods

hU-MSCs were isolated and characterized by specific surface markers. hU-MSCs were treated with isorhamnetin to precondition these cells. The migration potential of MSCs was analyzed by the in vitro scratch assay, while the healing potential of normal, and preconditioned MSCs was compared by transplanting them into a rat model of a second degree burn wound 72 h after burn injury and observed for 2 wk. Histological and gene expression analyses were performed on day 7 and 14 after cell transplantation to determine complete wound healing.

Research results

The in vitro scratch assay analysis showed that preconditioned hU-MSCs significantly reduced the scratch area at 24 h, and completely closed the scratch area at 48 h as compared to normal MSCs. The preconditioned MSCs showed reduced inflammation, remodeled epidermis and dermis without scar formation and regeneration of hair follicles as observed following histological analysis. Preconditioning of MSCs promoted angiogenesis and remodeling, and decreased apoptosis as observed by gene expression studies of the corresponding burn wounds.

Research conclusions

Preconditioning of hU-MSCs with isorhamnetin decreases wound progression by reducing inflammation, and improving tissue architecture and wound healing. The study outcome is expected to lead to an improved cell-based therapeutic approach for burn wounds.

Research perspectives

The current study will be useful for developing an effective treatment strategy for burn patients based on the synergistic effect of isorhamnetin and MSCs to accelerate wound healing with complete skin regeneration without scar formation.