Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2022; 14(3): 245-263
Published online Mar 26, 2022. doi: 10.4252/wjsc.v14.i3.245
Optimization of adipose tissue-derived mesenchymal stromal cells transplantation for bone marrow repopulation following irradiation
Min-Jung Kim, Won Moon, Jeonghoon Heo, Sangwook Lim, Seung-Hyun Lee, Jee-Yeong Jeong, Sang Joon Lee
Min-Jung Kim, Jee-Yeong Jeong, Department of Biochemistry, Cancer Research Institute Kosin University College of Medicine, Seo-gu 49267, Busan, South Korea
Won Moon, Department of Internal Medicine, Kosin University College of Medicine, Seo-gu 49267, Busan, South Korea
Jeonghoon Heo, Department of Molecular Biology and Immunology, Kosin University College of Medicine, Seo-gu 49267, Busan, South Korea
Sangwook Lim, Department of Radiation Oncology, Kosin University College of Medicine, Seo-gu 49267, Busan, South Korea
Seung-Hyun Lee, Department of General Surgery, Kosin University College of Medicine, Seo-gu 49267, Busan, South Korea
Sang Joon Lee, Department of Ophthalmology, Gospel Hospital, Kosin University College of Medicine, Seo-gu 49267, Busan, South Korea
Author contributions: Lee SJ and Jeong JY contributed to the conception and design of the study, data interpretation, and funding acquisition; Lee SH, Lim S, Moon W, and Kim MJ contributed to the methodology, data acquisition, and analysis; Lee SJ wrote the original draft of the article; Lee SJ, Jeong JY, and Heo J drafted, reviewed and edited the manuscript, and contributed to project administration and supervision; all authors read and approved the final version of the manuscript.
Supported by The Basic Science Research Program Through The National Research Foundation of Korea (NRF) Grant Funded By The Korean Government To Lee S.J., No. 2021R1F1A1052084.
Institutional review board statement: The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of Kosin University College of Medicine (KMAP-16-18) and all procedures for human adipose tissue were conducted with informed consent under the Kosin University Gospel Hospital IRB approval protocol (protocol number 09–36).
Institutional animal care and use committee statement: All animal experiments were approved by the Institutional Animal Care and Use Committee of Kosin University College of Medicine, and the animals were maintained and treated according to the regulations of the Association for Research in Vision and Ophthalmology.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
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: Sang Joon Lee, MD, PhD, Doctor, Professor, Department of Ophthalmology, Gospel Hospital, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu 49267, Busan, South Korea. hhiatus@gmail.com
Received: November 19, 2021
Peer-review started: November 19, 2021
First decision: December 12, 2021
Revised: January 12, 2022
Accepted: February 27, 2022
Article in press: February 27, 2022
Published online: March 26, 2022
Processing time: 126 Days and 0.1 Hours
Abstract
BACKGROUND

Bone marrow (BM) suppression is one of the most common side effects of radiotherapy and the primary cause of death following exposure to irradiation. Despite concerted efforts, there is no definitive treatment method available. Recent studies have reported using mesenchymal stromal cells (MSCs), but their therapeutic effects are contested.

AIM

We administered and examined the effects of various amounts of adipose-derived MSCs (ADSCs) in mice with radiation-induced BM suppression.

METHODS

Mice were divided into three groups: Normal control group, irradiated (RT) group, and stem cell-treated group following whole-body irradiation (WBI). Mouse ADSCs (mADSCs) were transplanted into the peritoneal cavity either once or three times at 5 × 105 cells/200 μL. The white blood cell count and the levels of, plasma cytokines, BM mRNA, and BM surface markers were compared between the three groups. Human BM-derived CD34+ hematopoietic progenitor cells were co-cultured with human ADSCs (hADSCs) or incubated in the presence of hADSCs conditioned media to investigate the effect on human cells in vitro.

RESULTS

The survival rate of mice that received one transplant of mADSCs was higher than that of mice that received three transplants. Multiple transplantations of ADSCs delayed the repopulation of BM hematopoietic stem cells. Anti-inflammatory effects and M2 polarization by intraperitoneal ADSCs might suppress erythropoiesis and induce myelopoiesis in sub-lethally RT mice.

CONCLUSION

The results suggested that an optimal amount of MSCs could improve survival rates post-WBI.

Keywords: Adipose tissue-derived stem cells; Bone marrow suppression; Mesenchymal stromal cells; Radiation; Cell therapy

Core Tip: Bone marrow (BM) suppression is one of the most common side effects of radiotherapy and the primary cause of death following exposure to irradiation. Although adipose tissue-derived stromal cell transplantation has emerged as a new treatment for BM suppression, the therapeutic effects are not proven conclusively. Our study showed that multiple transplantations of the adipose-derived mesenchymal stromal cells (ADSCs) delayed repopulation of BM hematopoietic stem cells. The administration of an optimal amount of ADSCs can improve survival rates following whole-body irradiation.