Page 25 - Human Umbilical Cord Mesenchymal Stem Cells

TISSUE ENGINEERING: Part B
Volume 26, Number 6, 2020
ª Mary Ann Liebert, Inc.
DOI: 10.1089/ten.teb.2019.0351

REVIEW ARTICLE

Mesenchymal Stem Cells for Chronic Wound Healing:

Current Status of Preclinical and Clinical Studies

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Yi-Zhou Huang, PhD, 1,2 Min Gou, MD, Lin-Cui Da, PhD, Wen-Qian Zhang, and Hui-Qi Xie, MD, PhD 1,2

Healing skin wounds with anatomic and functional integrity, especially under chronic pathological conditions,
remain an enormous challenge. Due to their outstanding regenerative potential, mesenchymal stem cells
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(MSCs) have been explored in many studies to determine the healing ability for difficult-to-treat diseases. In
this article, we review current animal studies and clinical trials of MSC-based therapy for chronic wounds, and
discuss major challenges that confront future clinical applications. We found that a wealth of animal studies
have revealed the versatile roles and the benefits of MSCs for chronic wound healing. MSC treatment results in
enhanced angiogenesis, facilitated reepithelialization, improved granulation, and accelerated wound closure.
There are some evidences of the transdifferentiation of MSCs into skin cells. However, the healing effect of
MSCs depends primarily on their paracrine actions, which alleviate the harsh microenvironment of chronic
wounds and regulate local cellular responses. Consistent with the findings of preclinical studies, some clinical
trials have shown improved wound healing after transplantation of MSCs in chronic wounds, mainly lower
extremity ulcers, pressure sores, and radiation burns. However, there are some limitations in these clinical trials,
especially a small number of patients and imperfect methodology. Therefore, to better define the safety and
efficiency of MSC-based wound therapy, large-scale controlled multicenter trials are needed in the future. In
addition, to build a robust pool of clinical evidence, standardized protocols, especially the cultivation and
quality control of MSCs, are recommended. Altogether, based on current data, MSC-based therapy represents a
promising treatment option for chronic wounds.

Keywords: mesenchymal stem cells, chronic wounds, clinical trials, stem cell-based therapy, regenerative
medicine

Impact Statement
Chronic wounds persist as a significant health care problem, particularly with increasing number of patients and the lack of
efficient treatments. The main goal of this article is to provide an overview of current status of mesenchymal stem cell
(MSC)-based therapy for chronic wounds. The roles of MSCs in skin wound healing, as revealed in a large number of
animal studies, are detailed. A critical view is made on the clinical application of MSCs for lower extremity ulcers, pressure
sores, and radiation burns. Main challenges that confront future clinical applications are discussed, which hopefully
contribute to innovations in MSC-based wound treatment.

Introduction diseases, such as diabetes and peripheral arterial diseases, can
cause refractory wounds. With rising rates of obesity and di-
kin covers the surface of human body, serves as a abetes, the incidence of chronic wounds is increasing rapidly.
Sprotective barrier against pathogens, and has vital roles in Severe damage of skin integrity renders the patients suscep-
human body homeostasis. Trauma, burns, and many chronic tible to major disability or even death. Furthermore, chronic

1
Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, State Key Laboratory of Biotherapy and Cancer
Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
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Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.
3
State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West
China Hospital of Stomatology, Sichuan University, Chengdu, China.
4 Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.
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