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Page 2 of 8 Kim et al. Plast Aesthet Res 2018;5:31 I http://dx.doi.org/10.20517/2347-9264.2018.26

a lipoma for autologous breast augmentation in 1895 and documented further cases of autologous fat trans-
[2,3]
fer . Case reports by Czerny, Bartlett, Lexer, Passot, Gurney, Peer, May, Miller and more were soon backed
by a scientific evaluation of fat grafting with investigators examining the high rate of fat resorption. March-
and performed a histological analysis on transplanted fat and found resorption and necrosis while Neuhof
hypothesized that transplanted fat tissue may necrotize and eventually be replaced by a mix of fibrous and
[4,5]
adipose tissue .
Contrary to the general perception that adipose tissue primarily acts as an energy storage with other rather
passive functions such as mechanical padding and thermal insulation, investigators revealed its complex
[6]
structure and its diverse cell composition . The liposuction technique, invented by the Italian gynecologists
[7]
Arpad and Giorgio Fischer, was soon popularized by Yves-Gerard Illouz . While Sydney Colemans defined
fat grafting protocol then established the era of lipofilling, it was the characterization of mesenchymal stem
[8,9]
cells within adipose tissue that lay the foundation to adipose-derived stem cell (ASC) therapy . ASC thera-
py is a modern approach in regenerative medicine that utilizes isolated ASCs for various indications includ-
ing wound repair. In this review, the most fundamental characteristics of ASCs, and insights into their role
in cutaneous wound repair based on recent experimental and clinical data will be presented.

CHARACTERISTICS OF ASCS
Enzymatic digestion of harvested fat tissue by collagenase separates adipose tissue into two fractions: a top
layer of floating mature adipocytes and a bottom layer of cells, that are collectively called the stromal vascu-
lar fraction (SVF). The SVF represents a heterogenous cell mixture including adipose tissue macrophages,
smooth muscle cells, T- and B-lymphocytes, endothelial cells, pericytes, myocytes, fibroblasts and impor-
tantly ASCs.

ASCs are mesenchymal stem cells of mesodermal origin with low oxygen consumption and a considerable
[9]
proliferation rate that differentiate into mesodermal, ectodermal and entodermal cell lines [Figure 1]. In
recent years, they have evolved as a serious alternative to bone marrow-derived stem cells (BMSC), the major
[10]
source for mesenchymal stem cells so far . In contrast to BMSCs, the harvest of ASCs is easier, and excit-
[11]
ingly, the relative yield of ASCs is reported to be substantially higher when compared to BMSCs . One mil-
[12]
liliter of human lipoaspirate will yield approximately (2.5-3.75) × 10 ASCs within a timeframe of 4-6 days .
5
The increasing interest in ASC and its applications have led to a non-transparent nomenclature that was ad-
dressed by the International Federation for Adipose Therapeutics and Science and the International Society
for Cellular Therapy (ISCT). As any other mesenchymal stem cell population, ASCs have to meet the mini-
mal criteria defined by the ISCT which encompass: plastic adherence, differentiation into the adipogenic,
[13]
chondrogenic, and osteogenic line as well as expression of specific surface genes . In addition, ASCs may
be distinguished from SVF cells and BMSCs by other distinct surface markers. ASCs consistently express
cluster of differentiation (CD) 73, CD90, CD105, CD44 and are negative for the endothelial markers CD31
and hematopoietic cell marker CD45; the population doubling capacity should be determined by the colony
[14]
forming unit fibroblast (CFU-F) assay .

ISOLATION OF ASCS
The regenerative potential of ASCs has rapidly attracted worldwide attention as their isolation and utili-
zation are easy and do not underlie the same legislative and ethical concerns as applicable to pluripotent
embryonic stem cells. In the first step, fat tissue is commonly harvested by lipectomy or liposuction proce-
dures. Although ASCs are not as vulnerable to high negative pressure as mature adipocytes (which tend to
[15]
rupture), higher suction pressure may significantly decrease ASC yield . Next, the aspirated adipose tissue
may undergo washing steps, e.g., with phosphate-buffered saline and collagenase digestion followed by colla-