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to TGF‑b as well as solutions that decrease the activity availability and fewer ethical issues, adult stem cells are
of connexin 43, a mediator of TGF‑b signaling, has been the most commonly used type of stem cells in medical
shown to reduce the inflammatory response and scar practice.
formation. [85,86] Evidence of success using TGF‑b‑related Mesenchymal stem cells are derived from bone marrow,
strategies was provided by a study showing that adipose tissue, umbilical cord, periosteum, tendons,
the exogenous addition to wounds of fibromodulin, muscle and skin. The most commonly used source
[96]
[87]
a TGF‑b modulator, reduces scar. Decorin is a small is adipose tissue. Stem cells affect all stages of wound
chondroitin/dermatan sulfate proteoglycan that limits the healing. They have significant anti‑inflammatory and
duration of TGF‑b influence on inflammation and tissue immunomodulatory effects in the inflammation phase of
repair, promoting regenerative repair and limiting tissue healing. In the proliferative phase, they also stimulate
[97]
fibrosis. Other novel strategies include the application fibroblasts, keratinocytes and endothelial cells, thereby
[88]
of antifibrotic human recombinant growth factors accelerating wound closure. Uysal et al. demonstrated
[98]
and cytokines, anti‑inflammatory substances, protease that wound healing time was reduced in rats treated
inhibitors and molecules that interfere with profibrotic by patchy skin grafts and mesenchymal stem cells. In
cytokine function (e.g. TGF‑b) and collagen synthesis at addition, wound contraction was reduced, angiogenesis
the wound site. [89] was increased, epithelialization progressed rapidly. [99]

FETAL WOUND HEALING Stem cell therapy can be administered either topically
or systemically. Falanga et al. [100] demonstrated a topical
application of mesenchymal stem cells with either
Fetal wound healing is an area of great interest because it fibrinogen or thrombin applied to chronic wounds in the
is characterized by scar‑less, regenerative wound healing. form of a spray. This spray is converted into a gel form
This process is age‑dependent, like postnatal healing, over the wound and helps in retaining the stem cells
wounds in third‑trimester cause scarring. The exact over the wound. [100] To improve the retention of stem
[90]
mechanism responsible for scar‑less healing in the first cells in the wound, cells are now applied on an adequate
and second trimesters is not yet clearly understood. The support/scaffold‑like collagen, skin substitutes. This helps
proposed mechanisms include decreased inflammation, in maintaining the viability of the cells and facilitates
unique properties of fetal cells, altered cytokine milieu, migration in the wound bed. [101]
[91]
variable gene expression and ECM deposition. Recent
fields of research revolve around the role of TGF, IL‑10 and CONCLUSION
mast cells. King et al. described a major role for IL‑10 in
[92]
scar‑less wound healing. The authors propose a “cytokine Cutaneous wound healing is a complex and dynamic
hypothesis” centered on the anti‑inflammatory properties biological process requiring the interaction and

of IL‑10. IL‑10 protects against excess deposition of coordination of many different cell types and molecules,
collagen, maintains elevated hyaluronic levels, enhances including growth factors and cytokines. Tremendous
fibroblast function, prevents differentiation of fibroblast strides have been made in delineating the myriad of
to myofibroblasts and increases survival of endothelial factors involved in normal and delayed/excessive healing.
progenitor cells and angiogenesis. Research in a mouse However, this increased understanding has not led to
[92]
model demonstrated the scarring potential of mast cells in significant advances in patient care. Administration of
fetal wounds. In early fetal life (day 15), scar‑less wounds exogenous growth factors and cytokines has shown
were associated with a lesser number of mast cells with promise in improving healing results in wounds. As wound
reduced degranulation as compared to later scarring healing involves multiple molecular mechanisms, no single
wounds. Another factor implicated in fetal wound agent therapy is likely to be successful in accelerating or
[93]
healing is the growth factor TGF‑b. Of the three isoforms, modulating wound healing.
TGF‑b1 is responsible for fibrosis. TGF‑b3 isoform is the
predominant isotype in fetal wound healing, and altered Financial support and sponsorship
profiling of the isoform may be a factor responsible for Nil.
scarless healing. Other additional mechanisms include Conflicts of interest
mediators of TGF pathway such as connective tissue There are no conflicts of interest.
growth factor, proteoglycan, decorin and P311. [94]
REFERENCES
ROLE OF STEM CELLS IN WOUND
HEALING 1. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999;341:738‑46.
2. Enoch S, Grey JE, Harding KG. Recent advances and emerging treatments.
BMJ 2006;332:962‑5.
Stem cells are a specialized group of cells with the potential 3. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res
for self‑renewal, as well as the ability to differentiate into 2010;89:219‑29.
various cell lineages. Stem cells can be classified according 4. Köse O, Waseem A. Keloids and hypertrophic scars: are they two different
to their origin (embryonic, fetal and adult) or based on sides of the same coin? Dermatol Surg 2008;34:336‑46.
the differentiation potential (totipotent, pluripotent, 5. Sen CK, Roy S. Wound healing. In: Rodriguez E, Losee J, Neligan PC, editors.
Plastic Surgery: Craniofacial, Head and Neck Surgery and Pediatric Plastic
multipotent and unipotent). Due to the ease of Surgery. 3rd ed. Vol. 3. Philadelphia: Saunders; 2012. p. 240‑66.
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254 Plast Aesthet Res || Vol 2 || Issue 5 || Sep 15, 2015