Mesenchymal stem cells show considerable potential as a means of treating idiopathic pulmonary fibrosis (IPF), but numerous issues need to be resolved before a stem cell approach might benefit patients.
The study, “Mesenchymal stem cells in the treatment of chronic lung disease,” published in the journal Respirology, also underscored that a deeper understanding of the cellular and molecular events leading to lung fibrosis will aid any attempts to use mesenchymal stem cells to slow or reverse the condition.
Researchers from the University of Pittsburgh School of Medicine conducted the study to offer an overview of the possibilities and challenges of using mesenchymal stem cell to treat lung fibrosis.
Increasingly, it is apparent that mesenchymal stem cells have properties that makes them suitable for such treatment: The cells are most often isolated from the bone marrow, and they are taken from the patient, minimizing the risk of immune reactions.
Early studies demonstrated that mesenchymal stem cells have immunomodulatory properties, preventing the expansion of T-cells. They also secrete anti-inflammatory immune cytokines, promoting an environment that is more suitable for tissue repair.
These cells also have the wondrous property of migrating to the site of tissue injury, where they can turn into several different cell types. In this way, they can rebuild many types of tissue. Even more valuable is the fact that the cells, when injected into animals as part of a preclinical study, were seen to seek out the lungs first, before migrating to other organs.
Studies have also shown that stem cells can transfer healthy mitochondria — the power plants of cells that are crucial to cell health — to damaged cells.
According to the authors, two drugs that are recent contributions to lung fibrosis care — Esbriet (pirfenidone) and Ofev (nintedanib) — only slow the disease progression, but are not able to reverse damage that is already present. There is, in other words, a great need for new treatments that could help people with lung fibrosis to survive beyond the few extra years that current drugs offer.
Animal experiments with mesenchymal stem cells for lung fibrosis have most often used the bleomycin-induced mouse model. Bleomycin is a chemical that triggers fibrosis, and mice exposed to the substance develop a condition resembling human IPF in many aspects.
Experimental results have shown that when mesenchymal stem cells are injected into mice exposed to bleomycin, they migrate to the damaged lungs and turn into epithelial-like cells. They also reduce inflammation by lowering the levels of inflammatory factors. And it is possible that more than just the injected cells are at work. Mesenchymal stem cells, found in fibrotic lungs of mice, secrete factors that can attract other bone marrow stem cells.
Importantly, the presence of the cells lower collagen deposits in the lung, limiting the development of fibrosis.
This beneficial course of events, however, was only seen when the cells were administered early in the disease course. In fact, one study found that mesenchymal stem cells can worsen fibrosis if given at latter disease stages.
Timing of treatment may be crucial, both for maximizing helpful effects and avoiding side effects, and more research establishing the optimal circumstances for stem cell delivery is needed.
Researchers are starting to investigate the potential of mesenchymal stem cells in people with IPF. Currently, five Phase 1 studies are registered in the clinical trials database clinicaltrials.gov.
One Phase 1b trial (NCT01385644), involving eight patients with moderate lung fibrosis, recently ended. The study, intended to analyze the safety, only found minor side effects of the procedure. During the six months the patients were followed, researchers also saw no evidence of worsening fibrosis.
The study by the Pittsburg researchers also underscores that, although anti-fibrotic effects of mesenchymal stem cell transplants have been observed in animals, clinical studies should focus their efforts on slowing disease progression, rather than reversing fibrosis, as this may be a more difficult goal to reach.
Scientists have also suggested that mesenchymal stem cells may be used in conditions of acute exacerbations in patients with lung fibrosis. As acute worsening states are linked to a more rapid deterioration, preventing the effects could add years to patients’ lives.