Mitochondrial Function Studied Using Decompression Sickness Conditions
Fibroblast Function in Connective Tissue
Fibroblasts are the most common cell type found in connective tissue throughout the body. Their main role is to produce the extracellular matrix and collagen fibers that support the connective tissue structure. In addition to their role in maintaining connective tissue, fibroblasts are also key players in wound healing. Following tissue injury, they migrate to the wound, proliferate, and generate extracellular matrix and collagen to repair the injured tissue. Importantly, fibroblast dysfunction is a key factor in conditions like fibrosis, cardiovascular disease, and Alzheimer’s.
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Lifeline® Fibroblasts in Current Research: Decompression Sickness
Decompression sickness (DCS) is a common cause of death due to diving. When a diver returns to the depressurized surface too quickly, gases, like nitrogen, can come out of solution and form bubbles in the tissues of the body, causing tissue damage. Although mitochondrial dysfunction has been implicated in DCS, the mechanism by which this occurs is not clear. In a 2018 study, Jang and colleagues at the University of Pennsylvania set out to determine how the conditions of DCS affect mitochondrial function using an in vitro model that simulates diving. Their model consisted of Lifeline® human dermal fibroblasts exposed to different gases under hyperbaric pressurized conditions, similar to what a diver would experience. They exposed cells to air, as well as nitrogen- or oxygen-rich gas mixtures, and compared mitochondrial function with that of control cells, which were not exposed to specialized gas mixtures or a pressurized environment.
First, the authors measured and compared cellular respiration rates of cells cultured in the four conditions. They found that routine respiration, or steady state respiration, was lowest in cells exposed to high oxygen conditions. Next, the group measured proton leak by treating cells with oligomycin, and demonstrated that cells exposed to high nitrogen had the most leak. Additionally, maximum respiration, or the maximum rate of oxygen consumption, was lowest in cells exposed to high oxygen levels. To determine whether the different gas mixtures affected mitochondrial dynamics, the researchers used wide-field fluorescence microscopy.
They found that mitochondrial motility was reduced in all groups compared with control, non-pressurized conditions. Additionally, mitochondrial fission (division of mitochondria) and fusion (merging of mitochondria) rates were not different between groups. Finally, the authors found that cells exposed to high oxygen conditions tended to have fewer mitochondria, and imaging for actin, a cytoskeletal protein, showed that different morphological changes occurred in response to the different gas mixtures.
Together, the results of this study demonstrate that under decompression conditions, different gas mixtures have different effects on mitochondrial function and dynamics.
Here on our blog, we highlight how researchers are using Lifeline® cells and culture models. Let us know how you use Lifeline® products and your published study could be next week’s feature!