Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2022; 14(12): 839-850
Published online Dec 26, 2022. doi: 10.4252/wjsc.v14.i12.839
Optimal concentration of mesenchymal stem cells for fracture healing in a rat model with long bone fracture
Myung-Seo Kim, Hyun-Ju Chung, Kang-Il Kim
Myung-Seo Kim, Kang-Il Kim, Department of Orthopaedic Surgery, School of Medicine, Kyung Hee University and Kyung Hee University Hospital at Gangdong, Seoul 05278, South Korea
Hyun-Ju Chung, Department of Core Research Laboratory, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, South Korea
Author contributions: Kim MS collected and assembled the data and performed data analysis and interpretation, manuscript writing; Chung HJ analyzed the data and performed interpretation; Kim KI provided the study material and designed the research study and performed final approval of manuscript; and all authors have read and approve the final manuscript.
Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea, No. HI20C1405.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Kyung Hee University Hospital at Gangdong (KHNMC 2022-11-017).
Institutional animal care and use committee statement: All procedures and treatments involving animals in this study followed the requirements of the Institutional Animal Care and Use Committee of the Clinical Research Institute, and the final approval was obtained from the ethics committee of Kyung Hee University Hospital at Gangdong (KHNMC AP 2020-018).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data underlying this article are available in the article and in its online supplementary material.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kang-Il Kim, MD, PhD, Professor, Department of Orthopaedic Surgery, School of Medicine, Kyung Hee University and Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul 05278, South Korea. khuknee@gmail.com
Received: September 27, 2022
Peer-review started: September 27, 2022
First decision: October 10, 2022
Revised: October 30, 2022
Accepted: December 7, 2022
Article in press: December 7, 2022
Published online: December 26, 2022
Processing time: 84 Days and 18.3 Hours
ARTICLE HIGHLIGHTS
Research background

Previous studies have reported that injection of mesenchymal stem cells (MSCs) improves fracture healing. However, no studies have specifically reported the most effective concentration of MSC.

Research motivation

There is no consensus on which concentration of MSCs to use for promoting fracture healing in a rat model of long bone fracture.

Research objectives

The present study aimed to assess the optimal concentration of MSCs for promoting fracture healing in a rat model.

Research methods

Wistar rats were divided into four groups according to MSC concentrations: Normal saline (C), 2.5 × 106 (L), 5.0 × 106 (M), and 10.0 × 106 (H) groups. New bone formation was evaluated using micro-computed tomography (micro-CT). Histological analysis was performed to evaluate fracture healing score. The protein expression of factors related to MSC migration and angiogenesis was evaluated using western blot analysis. The expression of cytokines associated with osteogenesis was evaluated using real-time polymerase chain reaction.

Research results

Micro-CT showed that new bone formation was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture. Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture. At 2 post-fracture, the protein expression levels of factors related to MSC migration and angiogenesis were significantly higher in groups M and H than in group L. The mRNA levels of cytokines associated with osteogenesis and angiogenesis were significantly higher in groups M and H than in group C at 6 wk post-fracture. There were no significant differences between M and H groups.

Research conclusions

Among the various concentrations used, 5.0 × 106 MSCs was the optimal concentration that promoted healing of long bone shaft fractures.

Research perspectives

This study could help to set the standard concentration of MSCs for evaluating fracture healing in an animal model of fracture.