Acute lung injury and acute respiratory distress syndrome remain major causes of death and suffering despite advances in management of these conditions. The incidence of these conditions is expected to double in the next 25 years, and treatment for it is largely supportive.
Fortunately, mesenchymal stem cells (MSCs) from bone marrow have been used in experimental models to treat lung injury in rodents. MSCs can engraft into lung tissue and become lung tissue (or at least turn into cells that sure look a whole lot like lung tissue). MSCs can also suppress the types of immune responses that tend to really chew up lung tissue. Thus, MSC administration seems to improve the condition of lungs that have been attacked by infections or damaging agents.
However, the rates at which MSCs engraft into lung tissue is rather low; too low, in fact, to account for the benefit provided by MSCs. Therefore, MSCs appear to help repair lung tissue by means of “paracrine” mechanisms. This 50-cent word simply means that MSCs repair the lung by secreting molecules that promote lung healing.
To test this hypothesis, researchers in the laboratory of Bernard Thérband from the Ottawa Hospital Research Institute in Ottawa, Canada has grown MSCs in culture, and used the growth medium after the MSCs had been removed from it to treat mice that suffered from lung injuries.
To induce lung injury, mice were treated with isolated bits of bacterial cells that are known to promote acute lung injury. Then a group of these lung-injured mice were treated with conditioned medium from bone marrow MSCs that had been grown in culture dishes.
The MSC-conditioned medium decreased lung inflammation, and disruptions of the blood vessels in the lung normally observed during lung injury. Therefore, the lungs did not fill up with liquid and pus. However, the conditioned medium did not prevent the weight loss associated with lung injury. The overall tissue architecture of the lung tissue was much more normal in the mice treated with the conditioned medium from MSCs than in the untreated mice. Conditioned medium from other cultured cells had no such sanative effect.
MSC conditioned culture media also modified the activity of white blood cells in the lung. Instead of charging forward into lung tissue and damaging it in response to damage, the white blood cells (so-called “alveolar macrophages”) worked with the lung tissue to help heal it.
Finally, when Thébaud and his colleagues examined the molecules secreted into the medium by the MSCs, they discovered that the culture medium was filled with lots of interesting molecules, but one in particular caught their eye: Insulin-like growth factor-1 (IGF-1). This molecule has all kinds of healing properties, and it seemed to Thébaud and company that IGF-1 could be responsible for a good portion of the healing. Therefore, they infused the lung-injured mice with purified IGF-1, and, wouldn’t you know, the lungs showed rather robust healing after being damaged with bacterial bits.
Thus MSCs provide lung healing properties and they do so by means of the molecules they secrete. Many of these healing properties can be recapitulated by infusing IGF-1.
Such experiments provide hope that future clinical trials for such treatments are not far off.