Transplantation Of Lung Stem Cells Improves Emphysema

In an animal model of emphysema, transplantations of their own lung-derived mesenchymal stem cells (MSCs) increased blood flow, oxygen transport and the synthesis of extracellular matrix. This approach could offer a potential alternative to conventional stem cell-based therapies for the treatment of emphysema.

Emphysema results from destruction of the tiny little sacs in the lung called alveoli. The alveoli surfaces are densely-packed with a network of delicate blood vessels. These blood vessels are the site of oxygen exchange. When a patient contracts emphysema, the walls of the alveoli break down and the tiny air sacs are transformed into a giant air sac. This provides far less surface area for the exchange of oxygen, and the patient has shortness of breath and difficulty catching their breath.

Edward P. Ingenito of Brigham and Women’s Hospital, who was part of this study, gave this perspective: “Mesenchymal stem cells are considered for transplantation because they are readily available, highly proliferative and display multi-lineage potential. Although MSCs have been isolated from various adult tissues, including fat, liver and lung tissues, cells derived from bone marrow (BM) have therapeutic utility and may be useful in treating advanced lung diseases, such as emphysema.”

According to the authors, previous transplantation studies that used bone marrow-derived MSCs and delivered them via an intravenous method have shown that such a treatment only marginally improves the condition of the lung. Also, therapeutic responses in those studies were limited to animal models of inflammatory lung diseases, such as asthma and acute lung injury. For this study, however, researchers isolated highly proliferative mesenchymal cells from adult lung tissue, and delivered them by means of an endoscopic delivery system that included the MSCs and a scaffold composed of natural extracellular matrix components.

According to Ingenito, “LMSCs display efficient retention in the lung when delivered endobronchially and have regenerative capacity through expression of basement membrane proteins and growth factors,”

Despite the use of autologous cells, only a fraction of the LMSCs delivered to the lungs alveolar compartment appeared to engraft. The lost likely reason for the low engraftment rates is due to the rates of cell death. Just as in the heart after a heart attack, diseased lungs represent a hostile environment, and this stressed the cells, which induced programmed cell death. The inability of the stressed cells to attach to their proper niches prevented them from surviving in the lung.

Even though the rates of engraftment were quite low, the findings of this study did suggest that LMSCs could contribute to lung remodeling and functional improvement 28 days after transplantation in 13 female sheep.  “Although the data is from a small number of animals, results show that autologous LMSC therapy using endoscopic delivery and a biocompatible scaffold to promote engraftment is associated with tissue remodeling and increased perfusion, without scarring or inflammation,” Ingenito said. “However, questions concerning mechanism of action and pattern of physiological response remain topics for future investigation.”
For the abstract of this study, see here.