Cell Therapy versus Lung Fibrosis
In recent years the research community has made some progress towards the use of cell therapies to treat fibrosis in lung tissue, the basis for a number of ultimately fatal conditions that present cannot be effectively controlled. Fibrosis is a disruption of the structure of tissue, the formation of scar-like structures that degrade tissue function. This line of research may soon be overtaken by the use of senolytic treatments to remove senescent cells, given that senescent cells appear to be a significant cause of the age-related failures in regenerative processes that cause fibrosis. Nonetheless, prior to recent work on cellular senescence and fibrosis, cell therapies were the most promising approach. Here, researchers report on recent progress in this part of the field:
Promising research points towards a possible stem cell treatment for several lung conditions, such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis. These diseases of the lung involve the buildup of fibrous, scar-like tissue, typically due to chronic lung inflammation. As this fibrous tissue replaces working lung tissue, the lungs become less able to transfer oxygen to the blood. In the case of IPF, which has been linked to smoking, most patients live for fewer than five years after diagnosis. The two drug treatments for IPF reduce symptoms but do not stop the underlying disease process. The only effective treatment is a lung transplant, which carries a high mortality risk and involves the long-term use of immunosuppressive drugs.
Scientists have been studying the alternative possibility of using stem cells to treat IPF and other lung fibrosis diseases. Some types of stem cells have anti-inflammatory and anti-fibrosis properties that make them particularly attractive as potential treatments for fibrotic diseases. Researchers have focused on a set of stem cells and support cells that reside in the lungs and can be reliably cultured from biopsied lung tissue. The cells are called lung spheroid cells for the distinctive sphere-like structures they form in culture. Lung spheroid cells showed powerful regenerative properties when applied to a mouse model of lung fibrosis. In their therapeutic activity, these cells also outperformed other non-lung-derived stem cells known as mesenchymal stem cells, which are also under investigation to treat fibrosis.
Researchers showed that they could obtain lung spheroid cells from human lung disease patients with a relatively non-invasive procedure called a transbronchial biopsy. They cultured lung spheroid cells from these tiny tissue samples until they were numerous enough - in the tens of millions - to be delivered therapeutically. When they infused the cells intravenously into mice, they found that most of the cells gathered in the animals' lungs. The researchers then induced a lung fibrosis condition in rats that closely resembled human IPF. Then the researchers injected the new cultured spheroid cells into one group of rats. Upon studying this group of animals and another group treated with a placebo, the researchers saw healthier overall lung cells and significantly less lung inflammation and fibrosis in the rats treated with lung spheroid cells.
The fact that these lung stem cells were injected intravenously but then homed into the lungs was interesting. Delivery could be one of the biggest challenges for stem cell therapy that actually repopulates stem cells niches. So elucidating this mechanism could be useful.