Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2020; 12(7): 676-687
Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.676
Application and prospect of adipose stem cell transplantation in treating lymphedema
Zhu-Jun Li, Elan Yang, Yun-Zhu Li, Zheng-Yun Liang, Jiu-Zuo Huang, Nan-Ze Yu, Xiao Long
Zhu-Jun Li, Elan Yang, Yun-Zhu Li, Zheng-Yun Liang, Jiu-Zuo Huang, Nan-Ze Yu, Xiao Long, Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Author contributions: Li ZJ and Long X designed the report; Li ZJ, Li YZ, Liang ZY, Huang JZ, and Yu NZ collected and evaluated the data; Li ZJ and Yang E analyzed the data and wrote the paper.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Xiao Long, MD, PhD, Professor, Surgeon, Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital of Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing 100730, China. pumclongxiao@126.com
Received: February 18, 2020
Peer-review started: February 18, 2020
First decision: April 25, 2020
Revised: May 8, 2020
Accepted: May 28, 2020
Article in press: May 28, 2020
Published online: July 26, 2020
Processing time: 158 Days and 20.3 Hours
Abstract
BACKGROUND

Lymphedema is a chronic, debilitating and incurable disease that affects 0.13%-2% of the global population. Emerging evidence indicates that adipose-derived stem cells (ADSCs) might serve as suitable seed cells for lymphatic tissue engineering and lymphedema therapy.

AIM

To summarize applications of ADSCs for treating lymphedema in both animal studies and clinical trials.

METHODS

A systematic search was performed on four databases – PubMed, Clinicaltrials.gov, the evidence-based Cochrane Library, and OVID – using the following search string: (“lymphedema” or “lymphoedema” or “lymphangiogenesis”) and (“adipose-derived stem cells” or “adipose-derived stromal cells” or “adipose-derived regenerative cells”). A manual search was performed by skimming the references of relevant studies. Animal studies and clinical trials using adipose-derived cells for the treatment of any kind of lymphedema were included.

RESULTS

A total of eight research articles published before November 2019 were included for this analysis. Five articles focused on animal studies and another three focused on clinical trials. ADSC transplantation therapy was demonstrated to be effective against lymphedema in all studies. The animal studies found that coadministration of ADSCs and controlled-release vascular endothelial growth factor-C or platelet-rich plasma could improve the effectiveness of ADSC therapy. Three sequential clinical trials were conducted on breast cancer-related lymphedema patients, and all showed favorable results.

CONCLUSION

ADSC-based therapy is a promising option for treating lymphedema. Large-scale, multicenter randomized controlled trials are needed to develop more effective and durable therapeutic strategies.

Keywords: Lymphedema; Adipose-derived stem cells; Animal model; Clinical trial; Vascular endothelial growth factor-C; Lymphangiogenesis

Core tip: Lymphedema is a growing global health problem. Adipose-derived stem cells might serve as suitable seed cells for tissue engineering of lymphatic vessels in vitro and in vivo. A systematic search of publications on the application of adipose-derived stem cells in the treatment of lymphedema identified five animal studies and three clinical trials. All eight studies showed improvement of lymphedema after treatment with adipose-derived stem cells. Animal studies conducted with acute lymphedema mouse models provided data for finding the proper dose and methods of administration. Clinical trials were conducted on breast cancer-related lymphedema patients and are important references for further application.