Fibrotic Disease Research Using Human Dermal Fibroblasts

Fibroblasts and Wound Healing

Fibroblasts are located in the connective tissue and produce the extracellular matrix, a supportive network that surrounds various cell types throughout the body. In addition to their role in tissue structure and support, fibroblasts also play a pivotal role in wound healing.

The skin is a very dynamic organ that is constantly exposed to various damaging conditions. When damage occurs to the skin, the process of wound healing begins with migration of fibroblasts to the wound site, where they produce new extracellular matrix. Once there, fibroblasts also proliferate and can convert to a myofibroblast phenotype. Myofibroblasts are specialized fibroblasts that have contractile function and are able to contract the wound edges to accelerate wound healing.

Interested in Lifeline® skin cell systems? Check out our catalog, which includes the following:

• Dermal microvascular endothelial cells- Adult and Neonatal
• Epidermal melanocytes – Adult and Neonatal
• Dermal fibroblasts – Adult and Neonatal
• Epidermal keratinocytes – Adult and Neonatal

New Research Using Lifeline® Human Dermal Fibroblasts

Abnormal myofibroblast activity contributes to multiple fibrotic diseases, including Dupuytren’s contracture. Dupuytren’s contracture is a condition that occurs in the hand, characterized by thickening of the fascia in the palm and contraction of the fingers, resulting in reduced mobility.

In a study this year, Doan and colleagues (opens in new window) set out to explore the inhibitory effects of glycated chitosan (GC) on myofibroblast contractile dynamics; in particular, they used a form of GC conjugated to single-walled carbon nanotubes (SWCTs). To test their hypotheses, the authors used a 3D anchored fibroblast-populated collagen matrix (aFPCM), an in vitro model system commonly used to study wound healing and fibrosis, cultured with Lifeline® human dermal fibroblasts and DC cell lines.

The group first tested the ability of GC to reduce compaction of the collagen matrix, which is correlated with myofibroblast activity. They found that chitosan and GC-containing aFPCM cultures exhibited less compaction (determined by higher aFPCM height) compared with controls. Using anchorage-released aFPCM cultures, the authors also found that chitosan and GC-containing aFPCM cultures displayed less tension.

Next, the authors assessed the effects of adding transforming growth factor beta (TGF-b1) —a stimulator of collagen matrix reorganization— to aFPCM cultures. Their results illustrated that TGF-b1 increased compaction and contraction, as well as myofibroblast proliferation and differentiation, in all conditions tested.

Together, the results of this study demonstrate that GC-SWNTs reduce myofibroblast contraction and tension generation, but are not sufficient to inhibit myofibroblast proliferation and differentiation.

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