Review Article
Stem Cell-Based Therapeutics to Improve Wound Healing
Michael S. Hu,1,2,3 Tripp Leavitt,1 Samir Malhotra,1
Dominik Duscher,1,4 Michael S. Pollhammer,4 Graham G. Walmsley,1,2
Zeshaan N. Maan,1 Alexander T. M. Cheung,1 Manfred Schmidt,4
Georg M. Huemer,4 Michael T. Longaker,1,2 and H. Peter Lorenz1
1
Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery,
Stanford University School of Medicine, Stanford, CA 94305, USA
2
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
3
Department of Surgery, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA
4
Section of Plastic, Aesthetic and Reconstructive Surgery, Johannes Kepler University, Linz, Austria
Correspondence should be addressed to Michael S. Hu; mhu2@stanford.edu
Received 21 July 2015; Revised 13 October 2015; Accepted 15 October 2015
Academic Editor: Nicolo Scuderi
Copyright 2015 Michael S. Hu et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Issues surrounding wound healing have garnered deep scientific interest as well as booming financial markets invested in novel
wound therapies. Much progress has been made in the field, but it is unsurprising to find that recent successes reveal new challenges
to be addressed. With regard to wound healing, large tissue deficits, recalcitrant wounds, and pathological scar formation remain
but a few of our most pressing challenges. Stem cell-based therapies have been heralded as a promising means by which to surpass
current limitations in wound management. The wide differentiation potential of stem cells allows for the possibility of restoring lost
or damaged tissue, while their ability to immunomodulate the wound bed from afar suggests that their clinical applications need
not be restricted to direct tissue formation. The clinical utility of stem cells has been demonstrated across dozens of clinical trials in
chronic wound therapy, but there is hope that other aspects of wound care will inherit similar benefit. Scientific inquiry into stem
cell-based wound therapy abounds in research labs around the world. While their clinical applications remain in their infancy, the
heavy investment in their potential makes it a worthwhile subject to review for plastic surgeons, in terms of both their current and
future applications.
1. Introduction
Wound healing is a complex process involving several physiological mechanisms coordinated in an effective response
to tissue injury. This process consists of several distinct, yet
overlapping phaseshemostasis and inflammation, proliferation, and maturationthat result in scar formation under
normal circumstances [1, 2]. Normal wound repair exists
along a spectrum of outcomes resulting from tissue injury.
These range from pathologic underhealing (i.e., chronic, nonhealing wounds) to pathologic overhealing (i.e., hypertrophic
scars and keloids), with physiologic healing, including scar
formation, somewhere in between. Interest in wound healing
research continues to grow, with much focus now directed
3
It is clear that there have been multiple attempts to
increase the effectiveness of wound healing techniques, as
well as creating more efficient and reliable grafts. Unfortunately, even the most advanced engineered skin substitutes demonstrate limitations; they are very expensive, are
not always effective, and cannot completely reconstitute
skin appendages. A different approach to wound healing is
therefore necessary to overcome current barriers in wound
therapy and create more pragmatic and effective solutions
to wound-related issues [27]. The pluripotent nature of stem
cells suggests that they may provide a means to overcome at
least some of the aforementioned barriers to optimal wound
management.
Conflict of Interests
The authors declare that there is no conflict of interests
regarding the publication of this paper.
Authors Contribution
Michael S. Hu, Tripp Leavitt, and Samir Malhotra contributed
equally to this work.
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