A secreted factor from bone marrow stem cells (BMSC-cm) improves the function of alveolar epithelial cells in repair and regeneration. These results support a potential therapeutic role for BMSC-cm released factors in idiopathic pulmonary fibrosis (IPF) and other lung diseases.
The study “Hepatocyte growth factor secreted by bone marrow stem cell reduce ER stress and improves repair in alveolar epithelial II cells” appeared in the journal Scientific Reports.
An impaired function of alveolar epithelial cells (those lining the alveoli of the lungs) is a key phenomenon in IPF, due to their capacity to secrete pro-fibrotic and pro-inflammatory factors. However, the mechanisms underlying a defective performance of alveolar epithelial cells are not completely understood.
Cells are composed of many intracellular organelles, which carry key functions for cell survival. One of these organelles is called the endoplasmic reticulum (ER), and previous studies found that a disturbance of the ER’s balance (homeostasis) activates a specific pathway to reestablish that balance. This loss of homeostasis is called ER stress and the pathway activated is called unfolded protein response (UPR).
“Evidence of endoplasmic reticulum (ER) stress has been reported in alveolar epithelial cells (AEC) in IPF patients,” the researchers wrote. Accordingly, “since ER stress mediates intracellular signaling pathways, it may be an essential therapeutic target to reduce or reverse tissue remodeling, stimulate epithelial repair, and initiate tissue regeneration in the fibrotic lung.”
Researchers investigated how ER stress impacts alveolar epithelial cells’ response to injury and the capacity to self-repair.
They first observed that alveolar epithelial cells from IPF patients show signs of ER stress. They also found that ER stress compromises the cells’ ability repair and proliferate.
Since “secreted mediators from bone marrow stem cells (BMSC-cm) have regenerative properties,” researchers hypothesized that BMSC-cm may reduce ER stress in alveolar epithelial cells. To test this hypothesis, they incubated alveolar epithelial cells from IPF patients with BMSC-cm, and observed that these cells reduced ER stress, enhanced cell proliferation and improved wound healing in alveolar epithelial cells.
Moreover, researchers pinpointed a single factor secreted by BMSC-cm, called hepatocyte growth factor (HGF), as the likely mediator for improved function of alveolar epithelial cells.
Overall, “our findings suggest that BMSC-secreted mediators may be used as pharmaco-therapeutics in future to restore ER homeostasis and improve alveolar epithelial repair and regeneration, a novel and promising new approach for lung repair and regeneration in fibrotic lungs,” the researchers concluded.