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World J Stem Cells. Jul 26, 2020; 12(7): 612-620
Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.612
Adipose-derived stem cell therapy shows promising results for secondary lymphedema
Li-Ru Hu, Jian Pan
Li-Ru Hu, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Li-Ru Hu, Jian Pan, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Hu LR wrote the paper and collected the data; Pan J and Hu LR approved the final version to be published.
Supported by The Project of Cadre Institution of Sichuan Province, No. 2019-901; and The Project of Human Resources and Social Security Department Academic and Technical Leader Training Fund in Sichuan, No. 2017-A.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
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: Jian Pan, PhD, Professor, Chief, Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Street, Chengdu 610041, Sichuan Province, China. jianpancn@163.com
Received: January 3, 2020
Peer-review started: January 3, 2020
First decision: February 19, 2020
Revised: March 29, 2020
Accepted: June 2, 2020
Article in press: June 2, 2020
Published online: July 26, 2020
Abstract

Lymphedema is mainly identified by progressive soft tissue swelling in impaired lymphatic system. Secondary lymphedema attributed to cancer therapy, parasite infection, and trauma remains a serious global disease. Patients with lymphedema suffer swelling, pain, and fatigue, with the dysfunction of the deformed extremities reducing the quality of life and increasing the risk of infection and lymphangiosarcoma. Adipose-derived stem cells (ADSCs) possess prominent regenerative potential to differentiate into multilineage cells, and produce various lymphangiogenic factors, making ADSC therapy a promising approach for lymphedema. The development of lymphedema consists of local inflammation, the fibrosis of lymphatic vessels, and the deposition of adipose fat. Existing animal models do not mimic the chronic inflammation environment, therefore suitable models are required in further studies. Some signal pathways and molecular mechanisms in physiological and pathological lymphagiogenesis remain unclear. In previous animal and human trials, ADSC therapy reduced edema in varying degrees. A larger number of trials with larger samples and longer follow-up periods are required to verify the efficiency and feasibility of ADSC therapy. ADSCs are of easy availability and immune exemption, making them a candidate for lymphedema treatment. Whether ADSCs enhance malignant characteristics or trigger the malignant change deserves further exploration and study before ADSC therapy can be made widely available.

Keywords: Secondary lymphedema, Adipose-derived stem cells, Lymphangiogenesis, Stem cells, Cell therapy, Lymphatic regeneration

Core tip: Secondary lymphedema attributed to cancer therapy, parasite infection, and trauma remains a serious global disease. Adipose-derived stem cells (ADSCs) possess prominent regenerative potential to differentiate into multilineage cells, and produce various lymphangiogenic factors, making ADSC therapy a promising approach for lymphedema. However, suitable animal models are required for further studies and a larger number of clinical trials are necessary to verify the efficiency and feasibility of ADSC therapy. This review exhibits the pathophysiology of lymphedema and elaborates how ADSCs can improve lymphatic function.