Human mesenchymal stem cells may be involved in keloid pathogenesis.
BACKGROUND
The pathogenesis of keloid is poorly understood. Although vigorous investigations have attempted to elucidate the mechanisms or causative factors of keloid, there are little data on why keloids are very intractable and recur easily in each patient.


METHODS
In an attempt to analyze the possible interaction between human mesenchymal stem cells and keloid-derived fibroblasts, the dual-chamber cell-migration assay, cell proliferation, ultrastructural morphology, and Western blot analysis were used to investigate the production of the extracellular matrices of the coculture.


RESULTS
Cell proliferation was not significantly different between keloid-derived fibroblasts and normal dermal fibroblasts during a 4-day observation period. There was a significant cell migration of human mesenchymal stem cells when keloid-derived fibroblasts were placed in the bottom chamber, compared to when normal dermal fibroblasts were placed in the same way in 8-microm diameter pore membranes (190.6 +/- 51.45 and 32.0 +/- 6.20 cells/field, respectively, P < 0.01). With 3-microm diameter pores, the human mesenchymal stem cells migrated in the pores only when the keloid-derived fibroblasts were placed in the bottom chambers (6.4 +/- 3.84 cells/field). Monolayer coculture of human mesenchymal stem cells and keloid-derived fibroblasts demonstrated further functional differentiation, such as collagen secretion and abundant rough endoplasmic reticulum. Western blot analysis of the cells in the modified dual-chamber culture demonstrated most significantly abundant fibronectin expression when the human mesenchymal stem cells contained keloid fibroblasts.


CONCLUSIONS
The results of this study may indicate that human mesenchymal stem cells participate and recruit in keloid pathogenesis by differentiating themselves toward keloid recalcitrant formation and progression.
Akino
Kozo
K
Division of Anatomy and Neurobiology, Nagasaki University, Nagasaki, Japan.
Akita
Sadanori
S
Yakabe
Aya
A
Mineda
Takao
T
Hayashi
Tomayoshi
T
Hirano
Akiyoshi
A
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002454:Cell Differentiation; D054443:Cell Migration Assays; D049109:Cell Proliferation; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D018870:Endoplasmic Reticulum, Rough / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007627:Keloid / Q000503:physiopathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D012867:Skin / Q000473:pathology; D055815:Young Adult
D005353:Fibronectins; D003094:Collagen