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J Dermatol Sci. 2016 Aug;83(2):95-105. doi: 10.1016/j.jdermsci.2016.03.003. Epub 2016 Mar 4.

Bone marrow derived mesenchymal stem cells inhibit the proliferative and profibrotic phenotype of hypertrophic scar fibroblasts and keloid fibroblasts through paracrine signaling.

Author information

1
Department of Aesthetic, Plastic, and Burn Surgery, Shangdong Provincial Hospital, Shangdong University, No. 324 Jing 5 wei 7 Road, Jinan 250021, China; Department of Plastic Surgery, People's Hospital of Jimo, No. 4 Jianmin Road, Jimo 266200, China.
2
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
3
Department of Plastic Surgery, People's Hospital of Jimo, No. 4 Jianmin Road, Jimo 266200, China.
4
Department of Aesthetic, Plastic, and Burn Surgery, Shangdong Provincial Hospital, Shangdong University, No. 324 Jing 5 wei 7 Road, Jinan 250021, China. Electronic address: huoran2015@126.com.

Abstract

BACKGROUND:

Hypertrophic scars and keloids, characterized by over-proliferation of fibroblasts and aberrant formation of the extracellular matrix (ECM), are considered fibrotic diseases. Accumulating evidence indicates that mesenchymal stem cells (MSCs) promote scar-free wound healing and inhibit fibrotic tissue formation, making them a potentially effective therapeutic treatment for hypertrophic scars and keloids.

OBJECTIVE:

To investigate the paracrine effects of bone marrow derived MSCs (BMSCs) on the biological behavior of hypertrophic scar fibroblasts (HSFs) and keloid fibroblasts (KFs).

METHODS:

Proliferative and profibrotic phenotype changes of the fibroblasts were analyzed by immunofluorescence staining, in-cell western blot, and real-time PCR.

RESULTS:

BMSC-conditioned medium inhibited HSF and KF proliferation and migration, but did not induce apoptosis. Interestingly, normal skin fibroblast-conditioned medium exhibited no inhibitory effects on HSF or KF proliferation and migration. Furthermore, BMSC-conditioned medium significantly decreased expression of profibrotic genes, including connective tissue growth factor, plasminogen activator inhibitor-1, transforming growth factor-β1, and transforming growth factor-β2, in HSFs and KFs at both transcriptional and translational levels. In contrast, the expression of antifibrotic genes, such as transforming growth factor-β3 and decorin, was substantially enhanced under the same culture conditions. Finally, we observed that BMSC-conditioned medium suppressed the ECM synthesis in HSFs and KFs, as indicated by decreased expression of collagen I and fibronectin and low levels of hydroxyproline in cell culture supernatant.

CONCLUSION:

These findings suggest that BMSCs attenuate the proliferative and profibrotic phenotype associated with HSFs and KFs and inhibit ECM synthesis through a paracrine signaling mechanism.

KEYWORDS:

BMSC; Hypertrophic scar; Keloid; Profibrotic; Proliferative

PMID:
27211019
DOI:
10.1016/j.jdermsci.2016.03.003
[Indexed for MEDLINE]

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