Mesenchymal stem cells derived from the bone marrow of people with idiopathic pulmonary fibrosis (IPF) perform basic cell functions, like growing and dividing, more poorly than do these cells from healthy people of the same age, a study reports.
The study, “Senescence of bone marrow-derived mesenchymal stem cells from patients with idiopathic pulmonary fibrosis,” published in the journal Stem Cell Research & Therapy, also drew attention to the disease’s “systemic consequences.”
A well-known risk factor for IPF is aging. Researchers have shown that lung cells from IPF patients show increased markers of cell senescence — an inability to continue to divide and grow — which is a hallmark of aging.
The cellular senescence theory of aging suggests that organisms, including people, age due to the accumulation of less physiologically useful senescent cells.
Senescence is the phenomenon by which normally proliferating and growing cells enter into a process called cell cycle arrest, no longer be dividing and producing more cells at a healthy rate.
Mesenchymal stem cells (MSCs) have been used in cell-based treatments for various diseases, as they have the ability to influence the immune system. These cells are also known to have a protective effect against IPF. But the normal workings of MSCs is known to decline with age as they enter into senescence.
Studies into animal models of lung injury have shown that infusing older bone marrow-derived MSCs (B-MSCs) is less effective — in terms of protective activity — than infusing B-MSCs derived from young donors.
Researchers here sought to determine differences in the characteristics of B-MSCs taken from healthy individuals and those of IPF patients within the same age range.
They looked for markers of cell senescence, as well measures of mitochondrial function (a measure of the cell’s viability), and DNA damage. Additionally, the protective ability of B-MSCs was investigated by infusing them into an animal model of IPF.
Results indicated that B-MSCs from IPF patients are more senescent than those of healthy people of the same age, with significant problems in mitochondrial function and a greater accumulation of DNA damage — amounting to poorer cell viability.
“We demonstrate for the first time that B-MSCs from IPF patients are senescent with significant differences in mitochondrial function, with accumulation of DNA damage resulting in defects in critical cell functions when compared with age-matched controls,” the team wrote.
Together, these aberrations led to failures in critical cell functions compared to controls.
Interestingly, the study also found that senescent IPF B-MSCs can induce senescence in fibroblasts of normal age by promoting inflammation.
“The consequences of having senescent B-MSCs are not completely understood, but the decrease in their ability to respond to normal activation and the risk of having a negative impact on the local niche by inducing inflammation and senescence in the neighboring cells suggests a new link between B-MSC and the onset of the disease,” its researchers wrote.
Finally, the researchers showed that B-MSCs from patients were less effective in preventing fibrotic changes in an animal model of the disease, underscoring their lesser protective powers compared to B-MSCs from healthy people.
“B-MSCs from IPF patients are defective when compared with age-matched controls,” the researchers concluded. And, they added, “[d]espite IPF being a disease with a respiratory phenotype and a major representation in the lung, our results show systemic consequences of the disease.”
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