Characterization of Lung‐specific Angiogenesis

Although recent significant advances in stem cell research and bioengineering techniques have made great progress in utilizing biomaterials to regenerate simple tissues in the orthopedic and periodontal fields, attempts to regenerate the structures and functions of more complex organs such as lungs have not been very successful. This may be partly because the biological processes of organ regeneration have not been well explored. Angiogenesis, the formation of new blood vessels, in specific organ plays key roles in organ regeneration. Therefore, the goal of this project is to recapitulate the lung‐specific microenvironments and replicate angiogenesis in a specific organ in situ in order to regenerate lungs in mice. Although conventional in vivo angiogenesis assays, such as subcutaneous implantation of extracellular matrix‐rich hydrogels (e.g., Matrigel), are extensively utilized to explore the general mechanisms of angiogenesis, lung‐specific angiogenesis has not been well characterized because the methods for implantation of biomaterials on the mouse lung have not been well established. Here we have developed a unique method to implant fibrin gel on the lung surface of living mouse, allowing for the successful recapitulation of host lung‐derived angiogenesis inside the gel. We also found that tumor‐derived angiogenic factor induced angiogenesis in the lung using a similar implantation method. Thus, this approach enables researchers to explore the mechanisms by which the lung‐specific microenvironment controls angiogenesis and alveolar regeneration in both normal and pathological conditions. This project is supported by American Heart Association and Boston Children's Hospital Career Development Award.