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RECONSTRUCTIVE

Fat Grafting and Adipose-Derived Regenerative


Cells in Burn Wound Healing and Scarring:
A Systematic Review of the Literature
Alexandra Condé-Green,
Background: There is an abundance of literature supporting the efficacy of
M.D.
fat grafting in aesthetic and reconstructive cases. There has been a recent
Andrew A. Marano, B.A.
emphasis on the regenerative capacity of adipose-derived stem cells and their
Edward S. Lee, M.D. utility in the improvement of wound healing and scarring provided by their
Tom Reisler, M.D. cytokine and growth factor profiles. Despite the wealth of evidence supporting
Leigh Ann Price, M.D. their efficacy, little attention has been paid to their utility in burn treatment.
Stephen M. Milner, The authors’ purpose was to provide an analysis of the literature regarding the
M.B.B.S., B.D.S., D.Sc. use of fat grafting and regenerative cells in the treatment of burn wounds to
Mark S. Granick, M.D. guide surgeons and scientists on their clinical use.
Baltimore, Md.; and Newark, N.J. Methods: A systematic review of the literature was performed by a thorough
search of 12 terms using the PubMed, Medline, and Cochrane databases. Two
hundred forty-one articles were subject to evaluation by predetermined inclu-
sion and exclusion criteria.
Results: Six murine and 12 human studies were selected, including case-con-
trol studies, case series, and case reports. They describe histologic and clinical
effects of fat grafting and regenerative cell therapy, including improvements in
burn scar size and texture, enhanced angiogenesis, decreased inflammation,
alleviation of pain, and return of function.
Conclusions: There is a dearth of randomized controlled trials and quantitative
analysis supporting the efficacy of fat grafting and adipose regenerative cells
in burns. However, the subjective improvements in scars are encouraging. The
authors hope that this review will be a foundation for future studies and will
highlight the breadth of knowledge yet to be explored by this therapy. (Plast.
Reconstr. Surg. 137: 302, 2016.)
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A
utologous fat grafting is a commonly used when liposuction increased the availability of fat
technique for treating volume and con- stores and allowed surgeons to experiment with
tour defects in aesthetic and reconstruc- the therapeutic potential of autologous fat.1
tive surgery. First described in the early 1900s, There has been a recent emphasis on not only
this procedure became popular in the late 1980s, the filling capability of fat but also its regenera-
tive capacity.2 The stromal vascular fraction of
From the Division of Burn Surgery, Department of Plastic and processed fat grafts contains multipotent stem
Reconstructive Surgery, Johns Hopkins University, School of cells that express adipogenic, osteogenic, and
Medicine; and the Division of Plastic Surgery, Department of chondrogenic genes.3 Many studies have demon-
General Surgery, Rutgers New Jersey Medical School. strated the angiogenic, immunomodulatory, and
Received for publication April 7, 2015; accepted August 27,
2015.
Presented at the Eighth International Workshop on Wound Disclosure: The authors declare no conflicts of
Technology, in Paris, France, January 18 through 20, interests with respect to the authorship and/or publica-
2015; and the Fifth International Fat Grafting Forum, in tion of this article. The authors received no financial
New Orleans, Louisiana, March 12 through 14. 2015. support for the research and/or authorship of this
Copyright © 2015 by the American Society of Plastic Surgeons article.
DOI: 10.1097/PRS.0000000000001918

302 www.PRSJournal.com
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Volume 137, Number 1 • Burn Wound Healing and Scarring

antiapoptotic capabilities of these cells, making using human fat, animal studies using animal
them a valuable and effective tool in restoring fat, clinical trials, and randomized controlled tri-
devitalized tissue, as evidenced by their efficacy als. Exclusion criteria were articles on fat graft-
in improving radiation-damaged skin.4,5 Adipose- ing for nonburn wounds, burn to a surface other
derived stem cells have also been shown to play a than skin (e.g., cornea, bone), fat transfer as part
role in antiaging6 and skin regeneration by form- of another graft (dermal grafts), and radiation
ing tissue consisting of hypodermis, dermis, and injury. Necessarily excluded were articles we were
epidermis.7 It is this regenerative capacity that is not able to access and those in languages other
of particular interest in burn wound therapy. than English, Portuguese, and French.
There is an abundance of literature support- A formal statistical analysis of the eligible
ing the efficacy of fat grafting in both aesthetic studies was not performed because of the meth-
and reconstructive cases. Recent studies have odologic and clinical heterogeneity. A detailed
shown the utility of adipose-derived stem cells in systematic review of the diverse outcomes was
the improvement of wound healing, describing undertaken instead.
their ability to regenerate soft tissues and their
remodeling capacity provided by their unique RESULTS
cytokine and growth factor profiles. Despite the
wealth of evidence supporting their efficacy in The primary search yielded 544 articles. After
wound healing, little attention has been paid to removal of duplicates, 241 of these were found to
their utility in the treatment of thermal injury. be distinct. The titles of remaining articles were
screened for relevance, after which 75 abstracts
The purpose of this study was to provide a thor-
were reviewed according to our inclusion crite-
ough analysis of the literature regarding the use
ria. The remaining 28 articles were read in their
of fat grafting and adipose-derived stem cells in
entirety and their references scoured for articles
the treatment of burn wounds to guide surgeons
that escaped our primary search criteria. Of these,
and scientists on their clinical use in burn wound
12 were excluded based on predetermined crite-
healing and scar remodeling, and in pursuing fur-
ria, and the remaining 16, along with one article
ther investigation.
that was discovered by review of references, were
included in this review (Fig. 1). Thus, we present a
PATIENTS AND METHODS total of 17 articles describing 18 studies, as one of
The foundation for this review was a system- the articles described two distinct studies.8
atic method for finding and evaluating the lit-
erature on the efficacy of fat and adipose stem Human Studies
cell therapy in the treatment of thermal injury. Twelve human studies were selected, includ-
A comprehensive search was conducted by two ing case control studies (n = 3), case series (n = 7),
independent reviewers in April of 2015 using the and case reports (n = 2). Adipose tissue was har-
following terms alone or in combination in the vested from one or multiple sites, including the
PubMed, MEDLINE, and Cochrane databases: abdomen (n = 9), trochanteric region (n = 3),
“burn,” “fat grafting,” “fat transplant,” “fat har- inner thigh (n = 1), and medial knee (n = 1), and
vesting,” “fat transfer,” “adipose stem cell,” “lipo- discarded burn tissue (n = 1). Adipose tissue was
filling,” “lipoinjection,” “lipotransfer,” “wound processed by high-speed centrifugation (n = 9)
healing,” and “scar treatment.” In addition, the and low-speed centrifugation (n = 2). Further
terms “exp burn/”and “exp adipose tissue/” were processing included mincing and processing for
used in MEDLINE to search all articles including adipose-derived stem cell isolation (n = 1), and
burn and adipose tissue exploded subheadings. supplementation of fat with stromal vascular frac-
Because one of the authors is fluent in Portuguese tion (n = 1) or platelet-rich plasma (n = 1).
and French, filters were set to include all articles
in English, Portuguese, and French. Case-Control Studies
Prospective inclusion criteria were the use of Bruno et al. conducted a study on 93 chronic
fat or adipose stem cell therapy and reporting of burns scars divided into two halves, where half
the effects on wound healing when used as an of each scar was treated with lipofilling and the
early intervention, the effects on scar formation other half served as a control.9 Improved vascu-
when used on an old wound, and the effects on larization of the dermal papillae and better colla-
quality of life. Studies included were case-control gen organization were shown in scars treated with
studies, case series, case reports, animal studies lipofilling after 6 months. There was a statistically

303
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Plastic and Reconstructive Surgery • January 2016

movement was seen as early as 3 months postop-


eratively in the fat-grafted side.
Gentile et al. compared fat grafts to fat-
enhanced grafts with stromal vascular fraction or
platelet-rich plasma in 30 patients with burn and
posttraumatic scars.10 In stromal vascular frac-
tion– and platelet-rich plasma–enhanced groups,
63 percent and 69 percent of wounds maintained
their volume after 1 year, respectively, compared
with 39 percent of the control group, indicating
less fat resorption in enhanced grafts.
The first case-control study9 was the strongest,
as clinical results following treatment with fat
grafting were corroborated by immunohistochem-
ical findings achieving statistical significance, and
clinical evaluation was double blinded. The sec-
ond case-control study8 showed objective statisti-
cally significant clinical findings in treated scars,
but there was no histologic confirmation. The
third study10 exposed three different preparation
techniques of fat grafting to scars and showed that
fat supplemented with stromal vascular fraction
or platelet-rich plasma achieved better contour
maintenance, with increased graft take. However,
they did not compare them to untreated controls
with no fat grafting.

Case Series
Fig. 1. Flow diagram of the search and selection strategy of Klinger et al. reported improvement in mimic
included articles. features, skin texture, and skin thickness in three
burn patients with facial hypertrophic scars and
keloids after fat injection into the dermohypoder-
significant decrease in S100-positive cells on mal junction performed twice, 3 months apart.11
immunohistochemistry, indicating that lipofill- Although findings were not compared to controls
ing correlates with reduction of melanocytes in or subjected to statistical analysis, new collagen
the wounds. There was a decrease in Langerin- deposition, increased vascularity, and dermal
positive cells, most likely resulting from efflux of hyperplasia were observed. Although the sample
trapped cells secondary to loose connective tis- size was small, the clinical results were corrobo-
sue. Increased visualization of Ki-67 in the basal rated with histologic findings.
layer of lipofilled wounds indicated that there was Caviggioli et al. performed fat grafting in the
increased proliferation. A modified Vancouver nipple-areola complex of 12 patients who specifi-
Scar Scale was used to provide objective clinical cally suffered burns to the chest.12 The average
evaluation of scars. Scores of 41 before treatment, nipple projection was 4.6 mm at 2 weeks, with
29 at 3 months, and 15 at 6 months were reported patients rating the results as excellent; and the
(range, 5 to 50, with low numbers representing projection was 2.9 mm at 2 years, with the major-
close to normal skin). ity rating the results as good. These were objec-
Klinger et al. conducted two separate studies tive clinical findings with a good follow-up period;
described in one article8 (which is reflected in a however, there was no control, histologic report,
footnote in Table 1).10–24 The case-control study or statistical analysis.
evaluated scars of 20 randomly selected patients. Brongo et al. reported evidence of new collagen
Each scar was treated half with fat and half with deposition, angiogenesis, and dermal hyperplasia
saline injection and evaluated by the Patient and in scars of 18 burned patients treated with lipo-
Observer Scar Assessment Scale25 and Durom- filling three times at 3-month interval.13 Improve-
eter measurement for scar firmness. Significant ments in texture, softness, thickness, and color of
improvement of color, shape, thickness, and treated scars based on a questionnaire completed

304
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Volume 137, Number 1 • Burn Wound Healing and Scarring

Table 1. List of Articles Included in This Systematic Review According to Inclusion and Exclusion Criteria,
Stratified by Level of Evidence
Level of No. of Subjects
Reference Study Type Evidence or Burn Scars
Human studies (n = 12)
Bruno et al., 20139 Case-control III 93 burn scars
Klinger et al.. 20138* Case-control III 20 patients with scars†
Gentile et al., 201410 Case-control III 30 patients with scars†
Klinger et al., 200811 Case series IV 3 patients with burn scars
Caviggioli et al., 201012 Case series IV 12 patients with burn scars
Brongo et al., 201213 Case series IV 18 patients with burn scars
Viard et al., 201214 Case series IV 15 patients with burn scars
Klinger et al., 20138* Case series IV 376 patients with scars†
Keck et al., 201315 Case series IV 5 patients with burns
Piccolo et al., 201516 Case series IV 240 patients†
Caviggioli et al., 200817 Case report V 1 patient with burn scar
Khouri et al., 201318 Case reports V 5 patients with burn scars†
Murine studies (n = 6)
Sultan et al., 201219 Murine — 20 mice
Shokrgozar et al., 201220 Murine — 10 rats
Huang et al., 201421 Murine — 30 rats
Loder et al., 201422 Murine — 20 mice
Karimi et al., 201423 Murine — 30 mice
Atalay et al., 201424 Murine — 20 rats
*Two studies were part of the same article.
†Three studies included burns and other types of wounds (trauma, ulcers).

by patients, surgeons, and external observers 1 year controls, was limited in number of cases, but rep-
after treatment were reported. Clinical improve- resents a novel technique with much potential.
ment of scars was supported by histologic findings Piccolo et al. described their 3-year experi-
with a good follow-up period, but there was no ence using fat grafting in acute and subacute burn
control, and no statistical analysis was conducted. wounds, and burn scars. They treated 240 patients
Viard et al. treated 15 patients with postburn who presented with burn, vascular, or traumatic
facial scars that had an average of 7.5 operations injuries. For acute and subacute wounds, fat was
1 year before fat grafting.14 Patients received two injected at 2- to 4-week intervals until a defini-
to three sessions. Subjective improvements in tive procedure such as skin graft or flap coverage
mimic features, skin texture, and skin thickness was performed. Subsequent scars were treated
were reported without controls or statistical analy- at 3-month intervals. The authors reported sub-
sis of the results. jective improvements in wound healing, fibrosis,
The second study of the 2013 article of Klinger and scar suppleness.16 This study was large, with
et al. reported improvements in scar elasticity, skin adequate follow-up, but lacked statistical analysis
softening, and mobility in periarticular regions and controls.
of 376 patients with retractile and painful scars
treated with lipofilling.8 This was a large study
where subjective clinical findings were reported; Case Reports
however, the authors did analyze a group of 20 Caviggioli et al. reported lasting correction of
patients that we mentioned above in the case-con- epiphora, xerophthalmia, and lagophthalmos, 1
trol study group. year after performing fat grafting in one patient
Keck et al. harvested adipose tissue from dis- with medial ectropion secondary to chemical
carded burn tissue. It was spread on a bovine col- burn.17 Khouri et al. reported scar softening and
lagen-elastin scaffold and applied on the fascia of increased range of motion after performing lipofill-
previously excised wounds covered with skin graft ing and percutaneous aponeurotomy (transform-
in five patients.15 Ninety percent of the skin graft ing a restrictive scar into a neomatrix scaffold into
was viable at postoperative day 10 in three patients. which fat grafts can settle) in patients with retractile
Flow cytometry, microscopy, and AdipoRed scars of the upper extremity, hands, and chest sec-
(Lonza, Walkersville, Md.) staining revealed that ondary to burns, radiation therapy, and congenital
adipose cells from debrided tissues were compa- restriction bands.18 Five of the patients presented
rable to abdominal fat in quantity, proliferative scars from burns, with objective measurement of
capacity, and differentiation. This study lacked functional improvement, but lacked controls.

305
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Plastic and Reconstructive Surgery • January 2016

Murine Studies fat grafts in 30 mice.23 The differences in eschar


Six murine studies assessing clinical and bio- thickness, inflammatory cell counts, epithelializa-
chemical outcomes of applying fat (n = 2) or adipose tion, and angiogenesis were not significant.
stem cells (n = 4) to burn wounds were selected. Atalay et al. showed statistically significant
Subjects were delivered burn injury by contact with decreased inflammation and fibroblastic prolifer-
a metal object submerged in hot water (n = 4) or by ation, and increased vascular endothelial growth
direct exposure to hot water (n = 2). The injury was factor expression, vascularization, and prolif-
located on a depilated dorsum (n = 5) or a hind paw erating cell nuclear antigen index (suggesting
(n = 1). Adipose tissue was harvested from mice or improved wound healing) in acute burns of rats
rats, as autografts (n = 5); or discarded human fat, injected with stromal vascular fraction.24 There
as a xenograft (n = 1). was no macroscopic evaluation of the wounds.
Sultan et al. conducted a controlled study The first three murine studies were con-
describing the physical and biochemical effects of ducted in burn scars,19–21 and the last three were
human fat on burn scars of 20 mice, where they conducted in acute burns showing the effects of
injected saline in one half and fat in the other. Fat- fat and adipose regenerative cells on wound heal-
grafted mice expressed significantly elevated levels ing.22–24 The last two studies had histologic results
of stromal cell–derived factor-1, vascular endothe- reported by pathologists that were blinded to
lial growth factor, and CD31 expression (indica- study groups (Tables 1 and 2).
tive of greater vascularity), and wound remodeling
expressed by transforming growth factor-β and DISCUSSION
matrix metalloproteinase-9, compared with con- Although limited in number, studies detailing
trols. They showed greater flux on laser Doppler the use of fat grafts or adipose-derived regenera-
scanning and less fibrosis.19 This study was the tive cells on burn wounds and scars have had posi-
strongest murine study, as there were untreated tive results. Murine studies have suggested that fat
control animals, and objective and statistically sig- grafting therapy can enhance vascularity, promote
nificant macroscopic and histologic evaluations. wound remodeling, and diminish neuropathic
Shokrgozar et al. supplemented collagen scaf- pain when administered weeks after injury.19,21 Such
folds with adipose-derived stem cells and showed epi- attributes are of particular utility when considering
dermal regeneration in burn wounds treated in 10 the common features of burn wounds: hypertro-
rats compared with controls.20 Wound surface area phic scars are characterized by an overactive prolif-
and histopathologic findings with formation of der- erative phase and an impaired remodeling phase of
mis and epidermis on the scaffolds supplemented wound healing,26 and neuropathic pain may occur
with adipose-derived stem cells were reported; how- in more than 50 percent of burn victims.27 Murine
ever, statistical analysis was not mentioned. studies have also suggested that adipose-derived
Huang et al. investigated the effects of autolo- stem cell therapy may improve outcomes when
gous fat on burn-induced neuropathic pain in applied on a newly acquired burn wound. Although
30 rats.21 Rats that received fat grafting had some studies had conflicting results regarding the
reduced burn-induced neuropathic mechanical effect on wound surface area, most concluded that
allodynia by suppression of phosphorylation of the early use of adipose-derived stem cell therapy
p38 in microglial cells. The clinical and histologic altered the course of the remodeling phase of heal-
findings were statistically significant, and there ing through decreased apoptosis22 and increased
were untreated controls. fibroplasia.23 Murine studies have limited applica-
Loder et al. studied the effects of isolated bility in human treatment; however, the human
autologous adipose-derived stem cells, fat, adipose- case-control studies, case series, and case reports
derived stem cells and fat, and phosphate-buffered have corroborating results.
saline grafts on burns of 20 mice.22 There was a sig- With regard to treatment of burn scars, histo-
nificant decrease in wound surface area in all groups logic analysis in human studies revealed that fat
compared to controls, but not to each other. Adi- grafting may increase vascularity, new collagen
pose-derived stem cells and mixed groups showed deposition, and reorganization.9,11,13 Studies also
significant decrease in wound depth apoptosis. reported improvements in mimic features, skin
Karimi et al. reported significant increases texture, thickness, color,11,13,14 and patient satisfac-
in fibroplasia and collagen remodeling and a tion.11,12,14 The utility of lipofilling as a secondary
decrease in surface area of wounds treated with measure to improve previous treatments is also
adipose-derived stem cells in comparison with considerable. Although the regenerative capacity

306
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Volume 137, Number 1 • Burn Wound Healing and Scarring


Table 2. Summary of Clinical, Macroscopic, and Microscopic Findings of Articles Reviewed, Including Advantages and Disadvantages of Each Study
Processing Acute Wounds Clinical/Macroscopic Microscopic
References Techniques vs. Scars Findings Findings Study Strengths Study Weaknesses
Human studies
Bruno et al., High-speed centrifugation Scars Functional and aesthetic Improved Comparison to controls No controls or
20139 improvement vascularization (half scar treated vs. half statistical significance
Increase patient of dermal papillae scar untreated) regarding objective
satisfaction score Better organization Double-blinded assessment clinical scores (Van-
of collagen of clinical evaluation couver Scar Scale and
Significant decrease Statistical significance for patient satisfaction
in S100-positive histology and IHC score)
cells and Langerin-Objective measurement of
positive cells clinical findings (Vancou-
ver Scar Scale) confirmed
by histologic findings
Adequate follow-up period
All scars resulted from burn
injury
Klinger et High-speed centrifugation Scars Pain relief, improved scar None reported Comparison to controls Scars resulting from vari-
al., 20138* elasticity, mimic features, (half scar injected with fat ous injuries (trauma,
mobility, filling of volume vs. half scar injected with after
deficits saline) surgery, radiotherapy,
Improved softness Randomized selection of burns)
(Durometer) patients
Improved POSAS Objective measurement of
clinical findings (POSAS
and Durometer)
Statistical significance for
clinical findings
Gentile et Three methods: Scars Restoration of contour No microscopic Comparison of multiple No comparison to
al., 201410 High-speed centrifugation Improved texture, softness evaluation of scars fat-processing techniques untreated controls
High speed centrifugation Improved patient satisfaction Objective measurement of Scars resulting from vari-
plus PRP contour maintenance by ous injuries (trauma
SVF enhancement MRI/ultrasound and burns)
Statistical significance of
clinical findings when
compared to nonen-
hanced fat grafting
Adequate follow-up
period (60 mo)
Klinger et High-speed centrifugation Scars Improved mimic features, New collagen One of the earliest Small sample size
al., 200811 skin texture, thickness deposition, studies showing (n = 3)
Soft-tissue contour increased local clinical improvement Lack of controls or
documented by MRI vascularity, dermal All scars resulted from statistical analysis
hyperplasia burn injury
Caviggioli et High-speed centrifugation Scars Improved nipple projection, None reported Objective measurement of Lack of controls or
al., 201012 skin texture, softness, clinical findings statistical analysis
color, elasticity Adequate follow-up (2 yr)
Improved patient satisfaction

(Continued )
307
Table 2. Continued

308
Processing Acute Wounds Clinical/Macroscopic Microscopic
References Techniques vs. Scars Findings Findings Study Strengths Study Weaknesses
Brongo et Low-speed centrifugation Scars Improved texture, softness, New collagen deposi- All scars resulted from burn Lack of controls or
al., 201213 thickness, color tion, injury statistical analysis
Reduction of scar contrac- neoangiogenesis, Adequate follow-up period
ture dermal hyperplasia (15 mo)
Improved symptomatology Objective measurement
per questionnaire of clinical findings (by
means of questionnaire)
Viard et High-speed centrifugation Scars Improved mimic features, None reported All scars resulted from burn Lack of controls or
al., 201214 skin texture, thickness injury statistical analysis
Improved patient satisfaction Lack of objective
clinical evaluation
Klinger et High-speed centrifugation Scars Pain relief, improved scar None reported Large sample size (n = 376) Lack of controls or
al., 20128* elasticity, mimic features, Added small group of statistical analysis
mobility in periarticular 20 patients analyzed Lack of objective
scars objectively, with statistical clinical evaluation
analysis (shown above*) Scars resulting from vari-
ous injuries (trauma,
after
surgery, radiotherapy,
burns)
Keck et ASC isolation (from Acute burns Improved skin graft Histology showed Novel therapeutic Lack of controls
al., 201315 débrided burn skin) take (n = 3) débrided burn technique Small sample
fat comparable to Potential for patients size (n = 5)
abdominal fat with large burn surface
Adipose tissue area
detected in recon-
structed areas
Piccolo et High-speed Acute, suba- Improved wound healing, Increase in elastic Large sample size (n = 240) Lack of controls or
al., 201516 centrifugation cute burns, fibrosis, scar suppleness fibers Adequate follow-up (3-yr statistical analysis
and scars experience) Lack of objective
clinical evaluation
Scars resulting from vari-
ous injuries (trauma,
ulcers, burns)
Caviggioli et High-speed Scars Correction of functional None reported Adequate follow up (1 yr) Small sample size
al., 200817 centrifugation deficits in periorbital One of the earliest studies (n = 1)
region showing clinical Lack of objective
Improved skin texture, improvement clinical evaluation
softness, elasticity
Khouri et Low-speed Scars Softened scar, increase None reported Objective measurement of Small sample size
al., 201318 centrifugation mobility, texture functional improvement (n = 5)
Lack of controls

(Continued )
Plastic and Reconstructive Surgery • January 2016

Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.

Volume 137, Number 1 • Burn Wound Healing and Scarring


Table 2. Continued
Processing Acute Wounds Clinical/Macroscopic Microscopic
References Techniques vs. Scars Findings Findings Study Strengths Study Weaknesses
Murine studies
Sultan et al., High-speed Scars Improved color, texture Increase CD31+ cells, Comparison to untreated
201219 centrifugation Greater flux by means of Picrosirius Red control animals
Doppler staining Objective macroscopic
Increased SDF-1, evaluation
VEGF, TGF-β, and Statistical significance for
MMP9 macroscopic and histo-
logic findings
Shokrgozar et ASC isolation Scars Improved wound Increased epidermal Comparison to untreated Lack of statistical
al., 201220 surface area regeneration controls analysis
Objective macroscopic
evaluation
Huang et al., Mechanical mincing Scars Decreased force Decreased p38+ and Comparison to untreated
201421 required to produce OX42+ cells controls
mechanical allodynia Increased collagen Objective macroscopic
deposition, evaluation
decreased cellu- Statistical significance for
larity clinical and histologic
findings
Loder et al., High-speed centrifugation Acute burns Decreased wound Decreased caspase Comparison of ASC, fat
201422 High speed centrifugation surface area staining and graft, fat plus ASC, and
plus ASC (all treatment groups) increased CD31 untreated controls
ASC Decreased wound (ASC and mixed Objective macroscopic
depth (ASC and groups) evaluation
mixed groups) Statistical significance for
macroscopic and histo-
logic findings
Karimi et al., Washing plus low- Acute burns Decreased wound surface Significantly Comparison of ASC, fat Lack statistical
201423 speed centrifugation area for ASC group increased fibro- graft, and untreated significance for
ASC (not significant) plasia, collagen controls macroscopic
remodeling Pathologist blinded to study findings
groups
Objective macroscopic
evaluation
Statistical significance for
histologic findings
Atalay et al., SVF isolation Acute burns None reported Decreased inflamma- Comparison to untreated Lack objective
201424 tion, fibroblastic controls macroscopic
proliferation, Pathologist blinded to study evaluation
increased groups
vascularization Statistical significance for
Increased PCNA histologic findings
index (wound
healing), VEGF
expression
IHC, immunohistochemistry; POSAS, Patient and Observer Scar Assessment Scale; PRP, platelet-rich plasma; SVF, stromal vascular fraction; MRI, magnetic resonance imaging; ASC, adipose-
derived stem cells; SDF-1, stromal cell–derived factor 1; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor; MMP9, matrix metalloproteinase 9; PCNA, proliferating
cell nuclear antigen.
309

*Two studies were part of the same article.


Plastic and Reconstructive Surgery • January 2016

Fig. 2. Effects of fat grafting and adipose-derived regenerative cells on burn wounds and scars. VEGF, vascular endothelial growth
factor; SDF-1, stromal cell–derived factor 1; TGF-β, transforming growth factor-β; MMP-9, matrix metalloproteinase 9.

of adipose-derived stem cells is an alluring con- does the availability of these adipose-derived stem
cept,28,29 there are notably few human studies cells from discarded burn tissue.
detailing the use of adipose-derived stem cell– Adipose-derived regenerative cells have been
supplemented grafts in burns.10,15 used in the treatment of other burn sequelae such
There were two human studies that investi- as heterotopic ossification.33 These studies were
gated wound healing in its acute phase. The large not included, as we focused on the effects on burn
series studied by Piccolo et al.16 showed improved wounds.
wound healing and fibrosis in acute and subacute Although nearly all documented uses of this
wounds. Although there was lack of controls, this therapy on burn wounds have had positive results,
article had pertinent details on the procedure, it should be noted that much of the current litera-
and adequate follow-up. The case series using ture consists of case reports or case series that lack
adipose cells from discarded burned tissue15 was rigorous statistical analysis (only two human stud-
a small case series that was difficult to assess, but ies included statistical analysis) or power. There
these cells were shown to share the adipogenic, has yet to be a large, prospective, randomized,
osteogenic, and chondrogenic potential of their controlled study detailing its use in patients with
abdominally derived counterparts.30–32 Therefore, burn wounds and scars.
they may represent a source of multipotent cells in We have attempted to summarize all articles
patients with extensive burns, for whom there may relevant to this subject. Our inclusion criteria
not be enough viable tissue to perform subcutane- were necessarily broad and our search terms were
ous liposuction to obtain such cells from nonin- diverse, and we included articles in languages
jured sites. Indeed, as the percentage of total body other than English. Still, we may have missed
surface area affected by burn injury increases, so studies that have been undertaken with the use

310
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Volume 137, Number 1 • Burn Wound Healing and Scarring

of fat grafting and burns. Even so, the results are radiation syndrome: Development of a new minipig model.
encouraging. Reports of clinical and histologic Exp Hematol. 2010;38:945–956.
6. Charles-de-Sa L, Gontijo-de-Amorim NF, Maeda Takiya C, et al.
improvements highlight the potential of this Antiaging treatment of the facial skin by fat graft and adipose-
therapy (Fig. 2), and show that much is yet to be derived stem cells. Plast Reconstr Surg. 2015;135:999–1009.
explored in this field. 7. Trottier V, Marceau-Fortier G, Germain L, Vincent C,
Fradette J. IFATS collection: Using human adipose-derived
stem/stromal cells for the production of new skin substi-
CONCLUSIONS tutes. Stem Cells 2008;26:2713–2723.
After careful review of the literature regarding 8. Klinger M, Caviggioli F, Klinger FM, et al. Autologous
fat graft in scar treatment. J Craniofac Surg. 2013;24:
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