Emphysema, bronchitis, asthma and cystic fibrosis are all diseases of the airways and they are the second leading cause of death worldwide. Over 35 million Americans alone suffer from chronic respiratory disease.
Scientists from the Weizmann Institute have now proposed a new direction for treating these diseases that might lead to a new method for alleviating some of their suffering. The study’s findings, which were published in Nature Medicine, show that it might be possible to use fetal stem cells to repair damaged lung tissue.
Particular stem cells normally found in the lungs are highly similar to those in the bone marrow. Organ-specific stem cells tend to be concentrated in special compartments rather than being distributed throughout the tissue. This insight prompted Prof. Yair Reisner of the Weizmann Institute’s Immunology Department to suggest: “That understanding suggested to us that we might be able to apply our knowledge of techniques for transplanting bone marrow stem cells to repairing lung tissue.”
Bone marrow transplants are based on two main principles: the ability of stem cells to navigate through the blood to the appropriate compartment and the prior clearing out of the compartment to make room for the transplanted stem cells. Dr. Reisner and his group thought it might possible to apply these principles to introducing new stem cells into the lungs. However, before they could do this, they needed to find a source of lung stem cells suitable for transplanting.
Reisner and his co-workers used fetal lung tissue from mice and humans (20–22 weeks of gestation for humans, and embryonic day 15–16 or E15–E16 for mice). Cells from these stages have differentiated into lung progenitor cells and are fully capable of lung regeneration. Reisner and his colleagues conducted a series of experiments in which they cleared the lung’s stem cell compartments with a new method developed on their own laboratory, and then were injected these new lung progenitor cells into mouse models of lung damage. The fetal lung stem cells found their way through the blood to the lungs and settled into the proper compartment. By six weeks, these cells were well on their way to differentiating into normal lung tissue. In these mice, their damaged lungs healed, and their breathing improved significantly.
Next, Reisner intends to determine the correct dosage of drugs that are needed to prevent rejection of the transplanted cells, which will be needed following such procedures. “But our real vision, bolstered by this success,” says Reisner, “is to create a bank of lung tissue that will be a resource for embryonic lung stem cells.” This bank could mean that there is a ready source of cells for repairing the damage in those with severe respiratory disease.
Reisner’s work shows that fetal lung progenitors can repopulate lungs and heal them. If Reisner can find a way to generate early lung progenitors from pluripotent stem cells, then such cells can be used to heal damaged lungs.