Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model.
BACKGROUND
Redundant collagen deposition at sites of healing dermal wounds results in hypertrophic scars. Adipose-derived stem cells (ADSCs) exhibit promise in a variety of anti-fibrosis applications by attenuating collagen deposition. The objective of this study was to explore the influence of an intralesional injection of ADSCs on hypertrophic scar formation by using an established rabbit ear model.


METHODS
Twelve New Zealand albino rabbits were equally divided into three groups, and six identical punch defects were made on each ear. On postoperative day 14 when all wounds were completely re-epithelialized, the first group received an intralesional injection of ADSCs on their right ears and Dulbecco's modified Eagle's medium (DMEM) on their left ears as an internal control. Rabbits in the second group were injected with conditioned medium of the ADSCs (ADSCs-CM) on their right ears and DMEM on their left ears as an internal control. Right ears of the third group remained untreated, and left ears received DMEM. We quantified scar hypertrophy by measuring the scar elevation index (SEI) on postoperative days 14, 21, 28, and 35 with ultrasonography. Wounds were harvested 35 days later for histomorphometric and gene expression analysis.


RESULTS
Intralesional injections of ADSCs or ADSCs-CM both led to scars with a far more normal appearance and significantly decreased SEI (44.04 % and 32.48 %, respectively, both P <0.01) in the rabbit ears compared with their internal controls. Furthermore, we confirmed that collagen was organized more regularly and that there was a decreased expression of alpha-smooth muscle actin (α-SMA) and collagen type Ι in the ADSC- and ADSCs-CM-injected scars according to histomorphometric and real-time quantitative polymerase chain reaction analysis. There was no difference between DMEM-injected and untreated scars.


CONCLUSIONS
An intralesional injection of ADSCs reduces the formation of rabbit ear hypertrophic scars by decreasing the α-SMA and collagen type Ι gene expression and ameliorating collagen deposition and this may result in an effective and innovative anti-scarring therapy.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, China. zhangqi0211@gmail.com.
Qi
Q
Zhang
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, China. linaliu98@163.com.
Li-Na
LN
Liu
Medical Science & Research Center, Beijing Shijitan Hospital, Capital Medical University, 10 Tie-Yi Road, Beijing, 100038, China. yongyiqiqi@aliyun.com.
Qi
Q
Yong
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, China. s25837@126.com.
Jing-Cheng
JC
Deng
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Shanghai, 200011, China. wgcao@sina.com.
Wei-Gang
WG
Cao
D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D017439:Cicatrix, Hypertrophic / Q000628:therapy*; D004195:Disease Models, Animal; D004423:Ear / Q000473:pathology*; D015552:Injections, Intralesional; D011817:Rabbits; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology