Chronic Lung Disease of Prematurity Pediatric Research and Clinical Trials

Stem cells provide partial protection for delicate lungs

Lung Stem CellPremature babies often need to be placed on ventilators, but these life-saving machines can sometimes damage their delicate lungs. In recent experiments in mice, stem cells taken from bone marrow and injected into the blood provided partial protection: the lungs’ blood vessels were better maintained and inflammation was reduced.

Even when fluid in which the cells (known as bone marrow stromal cells) were grown was able to protect the lungs – in fact, better than the stem cells themselves. Stella Kourembanas, MD, chief of Children’s Division of Newborn Medicine, believe this fluid, or certain proteins her lab has isolated within it, could become a future treatment to prevent preemies from developing chronic lung disease. She would also like to conduct follow-up experiments using stem cells taken from the umbilical cord, which can be obtained from infants in a less invasive manner than bone marrow cells.

Muhammad Aslam, MD, and Rajiv Baveja, MD, also of Newborn Medicine, were first authors on the study, published in the December 1 issue of the American Journal of Respiratory and Critical Care Medicine. Other members of the research team include Olin Liang, PhD, Angeles Fernandez-Gonzalez, PhD, Changjin Lee, PhD, and Alex Mitsialis, PhD.

Stem cell factors may prevent chronic lung disease

Success in preventing chronic lung disease in premature newborns has been limited. Researchers in Children’s Hospital Boston’s Division of Newborn Medicine hope that an experimental approach involving stem cells will lead to a new therapy—but not in the way one might expect.

The research team, led by Division Chief Stella Kourembanas, MD, Muhammad Aslam, MD, and Rajiv Baveja, MD, worked with newborn mice exposed to high concentrations of oxygen to model early chronic lung disease. They harvested bone-marrow stromal cells (BMSCs), a type of stem cell that has the potential to form lung cells, from the marrow of adult mice, and injected the cells into the newborns’ bloodstream. The cells found their way to the lungs and partially protected against injury: Blood vessels were better maintained and lung inflammation was prevented.

Intriguingly, tissue studies indicated that the lungs actually retained very few of the transplanted cells, suggesting that direct physical tissue repair wasn’t how the BMSCs protected the lungs. Further experiments suggested that the cells release factors that act in a paracrine manner, stimulating the lungs to heal themselves: When fluid from cultured BMSCs (the conditioned media) was injected by itself, the mice not only had better lung vascularization and reduced inflammation than untreated mice, they also showed healthy alveolar growth—something not seen with BMSCs themselves. “Being able to use the conditioned media would be far easier and more efficacious than using the stem cells themselves,” Dr. Kourembanas says.

A protein analysis of the media further revealed two abundant factors that are being tested directly: osteopontin and macrophage colony-stimulating factor 1. In the future, Dr. Kourembanas hopes to determine exactly how these and other factors released by stem cells protect the lungs, and whether they can reverse, not just prevent, chronic lung disease. She would also like to test conditioned media derived from human umbilical cord stem cells, eliminating the need to draw blood marrow from premature newborns.

The research was published in the December 1 issue of American Journal of Respiratory and Critical Care Medicine.