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): 659-675
Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.659
Role of stem cell therapies in treating chronic wounds: A systematic review
Anjali C Raghuram, Roy P Yu, Andrea Y Lo, Cynthia J Sung, Melissa Bircan, Holly J Thompson, Alex K Wong
Anjali C Raghuram, Roy P Yu, Andrea Y Lo, Cynthia J Sung, Melissa Bircan, Alex K Wong, Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, CA 90033, United States
Holly J Thompson, Wilson Dental Library, Herman Ostrow School of Dentistry of USC, Los Angeles, CA 90089, United States
Author contributions: Raghuram AC and Wong AK contributed to the study conception and design; Raghuram AC, Yu RP, Lo AY, Sung CJ, Bircan M and Thompson HJ contributed to literature review and analysis; Raghuram AC, Yu RP, Lo AY and Wong AK drafted, critically revised and edited the manuscript; Raghuram AC, Yu RP, Lo AY and Wong AK approved the final version.
Conflict-of-interest statement: While there is no conflict of interest relevant to this review article, we wish to disclose that Alex K. Wong’s laboratory receives research funding for pre-clinical wound healing studies from ACell, Inc.
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:
Corresponding author: Alex K Wong, MD, Associate Professor, Surgeon, Division of Plastic and Reconstructive Surgery, Keck School of Medicine of the University of Southern California, 1510 San Pablo Street, Los Angeles, CA 90033, United States.
Received: February 26, 2020
Peer-review started: February 26, 2020
First decision: April 22, 2020
Revised: May 3, 2020
Accepted: May 27, 2020
Article in press: May 27, 2020
Published online: July 26, 2020

The impairment of cutaneous wound healing results in chronic, non-healing wounds that are caused by altered wound environment oxygenation, tissue injury, and permissive microbial growth. Current modalities for the treatment of these wounds inadequately address the complex changes involved in chronic wound pathogenesis. Consequently, stem cell therapies have emerged as a potential therapeutic modality to promote cutaneous regeneration through trophic and paracrine activity.


To investigate current literature regarding use of stem cell therapies for the clinical treatment of chronic, non-healing wounds.


PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus were queried with combinations of the search terms “mesenchymal stem cells,” “adult stem cells,” “embryonic stem cells,” “erythroid precursor cells,” “stem cell therapies,” and “chronic wounds” in order to find relevant articles published between the years of 2000 and 2019 to review a 20-year experience. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (reviews, case reports/series, retrospective/prospective studies, and clinical trials) were evaluated by the authors for their depiction of clinical stem cell therapy use. Data were extracted from the articles using a standardized collection tool.


A total of 43 articles describing the use of stem cell therapies for the treatment of chronic wounds were included in this review. While stem cell therapies have been explored in in vitro and in vivo applications in the past, recent efforts are geared towards assessing their clinical role. A review of the literature revealed that adipose-derived stem cells, bone marrow-derived stem cells, bone marrow-derived mononuclear cells, epidermally-derived mesenchymal stem cells, fibroblast stem cells, keratinocyte stem cells, placental mesenchymal stem cells, and umbilical cord mesenchymal stem cells have all been employed in the treatment of chronic wounds of various etiologies. Most recently, embryonic stem cells have emerged as a novel stem cell therapy with the capacity for multifaceted germ cell layer differentiation. With the capacity for self-renewal and differentiation, stem cells can enrich existing cell populations in chronic wounds in order to overcome barriers impeding the progression of wound healing. Further, stem cell therapies can be utilized to augment cell engraftment, signaling and activity, and resultant patient outcomes.


Assessing observed clinical outcomes, potential for stem cell use, and relevant therapeutic challenges allows wound care stakeholders to make informed decisions regarding optimal treatment approaches for their patients’ chronic wounds.

Keywords: Mesenchymal stem cells, Adult stem cells, Embryonic stem cells, Erythroid precursor cells, Stem cell therapies, Chronic wounds

Core tip: Chronic wounds impose a significant burden on patients and the healthcare system with poor outcomes noted with the use of standard wound care protocols alone. Using stem cell therapies to treat these wounds results in improved cell signaling, release of growth factors and cytokines, neo-vessel formation, and immunomodulatory properties. Accordingly, patients experience enhanced healing of their formerly recalcitrant wounds. The objective of this review is to systematically evaluate the use of a wide range of stem cell therapies for the treatment of chronic wounds in order to guide providers in selecting appropriate treatment options for improved patient wound healing.