Generation of patient specific lung organoids from induced pluripotent stem cells
For patients with end stage lung disease currently the only treatment option is lung transplantation and there are not enough lungs available for everyone who needs them. In addition, rejection after lung transplantation is very common and the medicines taken to suppress the immune system often result in serious infections. We are proposing to use patient specific induced pluripotent stem cells and a novel bioengineering approach to make patient specific lung tissues for patients with poor lung function. The goal is to transplant these patient specific lung tissues into patients with lung diseases to improve their breathing and prevent the need for a lung transplant from an unmatched lung. We will make patient specific lung tissues as a potential development candidate and perform a preclinical test of these lungs in a small animal transplant model.
There are millions of people in the USA who suffer from lung diseases. The lungs have tremendous reserve, so that it is not until many years after lung injury that respiratory symptoms become manifest. California, the most populous state, is also the state with the largest number of people 65 years of age and over (3.6 million people in the year 2000) and therefore the prevalence of severe lung diseases in the USA is highest in California with a conservative estimate of over 100,000 cases. Of these, the worst cases develop end stage lung disease and either succumb to their disease or undergo a lung transplant. There were 190 lung transplants in California in 2012 and many more patients on the waiting list. Yet, most of the patients who were fortunate enough to receive a lung transplant will not be disease free, as 50% of them will develop rejection of their lung and they are all at risk for severe infections from the medications that reduce the immune system to try to prevent rejection. We are proposing to develop small lung organs from patient specific induced pluripotent stem cells that could be transplanted into patients to help them breathe without any risk of rejection and therefore without the need for medications to reduce the immune system. This would therefore be a ground breaking new treatment for patients with severe lung diseases and will greatly benefit the people of California with lung diseases.