Tissue engineering for in vitro analysis of matrix metalloproteinases in the pathogenesis of keloid lesions.
OBJECTIVE
Keloid lesions form because of alterations in the mechanisms that govern cutaneous wound healing. Although matrix metalloproteinases (MMPs) have been implicated in keloid pathophysiology, many questions still remain about their involvement. Our incomplete understanding of keloid pathophysiology has led to high recurrence rates in current treatments. No reliable animal model is available for studying keloids.


OBJECTIVE
To gain a better understanding of the disease mechanisms involved in keloid lesions in the hopes of identifying therapeutic options.


METHODS
Fibroblasts derived from keloid tissue were incorporated in either Matrigel or polyethylene glycol diacrylate mixed with type I collagen to create 3-dimensional models to investigate the role MMPs play in keloid formation. The MMP gene expressions were also compared between fibroblasts isolated from different sites within the same keloid lesion.


METHODS
The Johns Hopkins School of Medicine, Baltimore, Maryland.


METHODS
Keloid fibroblasts were received from the Baylor College of Medicine, and additional keloid fibroblasts were enzymatically isolated from the dermal layer of lesions removed from consenting patients at The Johns Hopkins Hospital.


RESULTS
In the Matrigel system, MMP9 and MMP13 were observed to be significantly upregulated in keloid fibroblasts. The addition of decorin resulted in a significant decrease of type I collagen and MMP1, MMP9, and MMP13 gene expressions from keloid fibroblasts. Higher MMP gene expressions were observed in fibroblasts isolated from the margins of the original keloid wound.


CONCLUSIONS
MMP9 and MMP13 are expressed significantly more in keloid-derived cells, thus making them 2 potential targets for disease modification. Molecules that target organization of the lesion's matrix can be beneficial in downregulating increased markers during the disease. In addition, heterogeneity is observed with the varying MMP gene expressions from site-specific fibroblasts within the same keloid lesion.
Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland.
Hanwei
H
Li
Zayna
Z
Nahas
Felicia
F
Feng
Jennifer H
JH
Elisseeff
Kofi
K
Boahene
D001672:Biocompatible Materials; D015415:Biomarkers / Q000378:metabolism; D003094:Collagen; D024042:Collagen Type I; D004338:Drug Combinations; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D007627:Keloid / Q000201:enzymology*; D007797:Laminin; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D011092:Polyethylene Glycols; D011509:Proteoglycans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
D001672:Biocompatible Materials; D015415:Biomarkers; D024042:Collagen Type I; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C437167:poly(ethylene glycol)diacrylate; C059485:matrigel; D011092:Polyethylene Glycols; D003094:Collagen; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9