PMID- 32282497
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210514
IS  - 1536-3708 (Electronic)
IS  - 0148-7043 (Print)
IS  - 0148-7043 (Linking)
VI  - 84
IP  - 5
DP  - 2020 May
TI  - Extracellular Vesicles Derived From Human Adipose-Derived Stem Cell Prevent the 
      Formation of Hypertrophic Scar in a Rabbit Model.
PG  - 602-607
LID - 10.1097/SAP.0000000000002357 [doi]
AB  - BACKGROUND: Preventing scar formation during wound healing has important clinical 
      implications. Numerous studies have indicated that adipose-derived stem cell 
      culture mediums, which are rich in cytokines and extracellular vesicles (EVs), 
      regulate matrix remodeling and prevent scar formation after wound healing. 
      Therefore, using a rabbit scar model, we tried to demonstrate which factor in 
      adipose-derived stem cell culture mediums plays a major role in preventing scar 
      formation (EVs or cytokines), as well as revealing the underlying mechanism. 
      METHODS: Human adipose-derived stem cells (hASCs) were isolated from the 
      subcutaneous adipose tissue of a healthy female donor. The surface CD markers of 
      third-passage hASCs were analyzed by flow cytometry. The adipogenic 
      differentiation capacity of the hASCs was detected using Oil O staining. A 
      cultured medium of third- to five-passage hASCs was collected for EV and EV-free 
      medium isolations. Extracellular vesicles were characterized using transmission 
      electron microscopy, NanoSight, and the Western blotting for surface markers 
      CD63, TSG101, and Alix. The EV-free medium was characterized by Western blotting 
      for vascular endothelial growth factor A (VEGFA), platelet derived growth factor 
      B (PDGFB), and transforming growth factor beta 1 (TGFbeta1). Eight-millimeter-diameter 
      wounds were created on the ventral side of both ears of 16 New Zealand rabbits. A 
      total of 0.1 mL of the human adipose-derived stem cell-extracellular vesicle 
      (hASC-EV) or EV-free medium was locally injected into wounds made on the right 
      ears during wound healing. Meanwhile, equal amounts of phosphate buffer saline 
      were injected into the left ears as a control. Biopsies of the wounded skin and 
      surrounding tissue were excised on postoperative day 28 and subjected to 
      hematoxylin and eosin (H&E), Masson, and alpha-SMA immunofluorescence staining. The 
      protein expression of alpha-SMA and collagen I in both scar tissues and the normal 
      skin were evaluated via Western blotting. RESULTS: The hASCs expressed high 
      levels of 49d, CD90, CD105, and CD73 but did not express CD34 or CD45. The hASCs 
      differentiated into adipocytes under an adipogenic induction medium. Under 
      transmission electron microscopy, the hASC-EVs were circular, bilayer membrane 
      vesicles and approximately 95% of the particles were between 50 and 200 nm in 
      size. The hASC-EVs expressed the same surface markers as EVs, including CD63, 
      TSG101, and Alix and displayed little expression of VEGFA, PDGFB, and TGFbeta1. The 
      EV-free medium had a high expression of VEGFA, PDGFB, and TGFbeta1 but displayed no 
      expression of CD63, TSG101, and Alix. In vivo, the hASC-EV treatment prevented 
      the formation of hypertrophic scars on postoperative day 28 and suppressed 
      collagen deposition and myofibroblast aggregation. However, the EV-free medium 
      did not prevent the formation of hypertrophic scars on the same time point and 
      had little effect on collagen deposition and myofibroblast aggregation when 
      compared with the control group. CONCLUSIONS: Our study suggests that hASCs are 
      associated with preventive scar formation therapy because of paracrine EVs rather 
      than cytokines. A local injection of hASC-EVs during wound healing efficiently 
      prevented hypertrophic scar formation, which may have a clinically beneficial 
      antiscarring effect.
FAU - Zhu, Yuan-Zheng
AU  - Zhu YZ
AD  - From the Department of Plastic Surgery, The Second Affiliated Hospital of 
      Nanchang University, Jiangxi, P.R. China.
FAU - Hu, Xuan
AU  - Hu X
FAU - Zhang, Jing
AU  - Zhang J
FAU - Wang, Zhao-Hui
AU  - Wang ZH
FAU - Wu, Shu
AU  - Wu S
FAU - Yi, Yang-Yan
AU  - Yi YY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Plast Surg
JT  - Annals of plastic surgery
JID - 7805336
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Adipocytes
MH  - Animals
MH  - *Cicatrix, Hypertrophic/etiology/prevention & control
MH  - *Extracellular Vesicles
MH  - Female
MH  - Humans
MH  - Rabbits
MH  - Stem Cells
MH  - Vascular Endothelial Growth Factor A
PMC - PMC7357540
COIS- Conflicts of interest and sources of funding: This work was supported by grants 
      from the National Natural Science Foundation of China (81660326), Natural Science 
      Foundation of Jiangxi Province (20171ACB20037), Youth Natural Science Foundation 
      of Jiangxi Province (20192BAB215028), and Youth Science Foundation of the Second 
      Affiliated Hospital of Nanchang University (2019YNQN12021). The authors declare 
      no conflicts of interest.
EDAT- 2020/04/14 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/07/13
CRDT- 2020/04/14 06:00
PHST- 2020/04/14 06:00 [entrez]
PHST- 2020/04/14 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/07/13 00:00 [pmc-release]
AID - 00000637-202005000-00025 [pii]
AID - SPA51830 [pii]
AID - 10.1097/SAP.0000000000002357 [doi]
PST - ppublish
SO  - Ann Plast Surg. 2020 May;84(5):602-607. doi: 10.1097/SAP.0000000000002357.