Paracrine factors from aggregates of fibroblasts or bone marrow stromal cells enhance skin wound healing
Year: 2012
Type: dissertation
Abstract: The skin is the largest organ of the human body. It maintains body homeostasis and provides an essential barrier that protects us from the environment. After injury to the skin, a complex series of tightly controlled responses are initiated to restore its integrity. In large-scale wounds, such as burns, the intrinsic capacity for healing is compromised due to lack of dermal support. Dermal fibroblasts guide crucial re-epithelialization events such as keratinocyte migration and proliferation. Fibroblast-keratinocyte interaction is directed by paracrine factors as well as cell-cell and cell-extracellular matrix contacts. Fibroblasts as well as other mesenchyme-derived cells such as bone marrow stromal cells can produce a vast array of growth factors in vitro. When activated by deprivation of extracellular matrix cell adhesion sites, the cells prefer cell-to-cell contacts, form clusters, and release growth factors. This present work focused on characterizing the use of a combination of growth factors released by mesenchymal cell aggregates, a process designated as nemosis, for treatment of skin wound healing. We used inhibitors of several intracellular signaling pathways to define the migration-inducing mechanisms of nemosis using a keratinocyte wound-healing assay. Model human keratinocytes HaCaT-cells responded to the nemosis-derived conditioned medium with enhanced migration, proliferation, and viability. A c-Met-specific small molecule tyrosine kinase inhibitor as well as an anti-hepatocyte growth factor antibody inhibited these responses. The study aimed to characterize means of improving wound healing by combining biological materials, such as fibrin or recombinant human collagen III with the growth factors to construct a transplantable cell- and growth factor-containing matrix. When we treated porcine partial-thickness wounds with the growth factor-containing fibrin matrix, we observed an increase in the proliferation and migration of hair-follicle and lateral wound-edge keratinocytes. In addition, granulation tissue formation was enhanced when compared with formation on saline-treated wounds. Keratinocyte transplantation in porcine full thickness wounds was feasible with a recombinant human collagen type III matrix. The results presented here indicate that cell-cell contact-activated fibroblasts or bone marrow stromal cells improve keratinocyte transplantation with paracrine factors. Fibrin or recombinant human collagen III can serve as vehicles for delivery of these signals to the target site in acute wounds. Since these factors are also crucial for healing of chronic non-healing wounds, it is likely that our therapeutic approach will be of benefit in their treatment, too.
Source: Työväentutkimus Vuosikirja
Author: Matti Peura
Language: English
Topic: Wound Healing and Treatments
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2144489169