Center for Engineered Whole Organs

	Rat liver decellularization process: left panel is rat liver before decellularization, middle panel is rat liver in process of decellularizing, and right panel is complete decellularization of the rat liver.

	Engineered lung, explanted after 3-hour transplantation. RBC in airways indicate inadequate barrier. — Photo courtesy of Niklason laboratory.
	Perfusion Decellularization of a Porcine Heart. The ascending aorta is canulated, the heart is then perfused with decellularization and washing solutions. Porcine heart before (top) and after (bottom) decellularization.
	Decellularized lung, photo courtesy of the Gilbert laboratory.

The mission of the Center for Engineered Whole Organs (CEWO) is to develop the methods and tools that will lead to successful implantation of engineered whole organs and complex tissues.

The initial focus is on the liver, lung and heart.  The primary research is led by internationally recognized scientists at three different academic institutions and there are nine additional collaborative projects-each at another institution. 

Need:

There is a long standing unmet need for patients suffering from end stage organ failure and the unchanging and unacceptable shortage of available donor organs. The definitive treatment for end stage organ failure is orthotropic transplantation.

However, the critical shortage of donor organs leads to increased morbidity and mortality for tens of thousands of patients each year. Approximately 27,000 deaths occur annually in the United States alone for patients with end stage liver disease, 120,000 patients due to chronic lung disease, 112,000 from end stage kidney failure, and 425,000 from coronary heart disease.

When one considers the additional patients who die waiting for heart or kidney transplants, the numbers become staggering. Those patients fortunate enough to receive an organ are burdened with the risk of chronic rejection and the morbidity associated with a lifelong regimen of immunosuppressant therapy. Although significant advances have been made in the development of engineered tissues such as blood vessels, urinary bladder, and trachea, none of these tissues require an intact vascular network that can be connected to the host circulation at the time of implantation. Whole organ constructs such as heart, lung, and liver will require this type of immediate vascular supply.  A successful regenerative medicine and engineering strategy for whole organ replacement would represent a quantum leap forward in the treatment of patients with end stage organ disease.

Opportunity:

In recent years a promising approach for functional organ replacement has emerged.  Decellularization of allogeneic or xenogeneic donor organs such as heart, liver, and lung provides an acellular, naturally occurring three dimensional biologic scaffold material that subsequently can be seeded with either functional differentiated parenchymal cells or selected progenitor cell populations.  Self assembly of these seeded cells with the aid of a three dimensional matrix has been shown to result in the formation of functional tissue in short term preclinical animal models.  This approach provides the opportunity for direct connection to the patient vasculature in either an orthotopic or heterotopic location.  Numerous challenges for this three dimensional organ engineering approach remain and are the focus of this center.

Conventional methods for addressing this severe shortage of donor organs and tissues have made minimal progress for the past several decades. Interest in the native three dimensional extracellular matrix (ECM) as a preferred scaffold substrate for functional tissue reconstruction has exploded in the past decade and there are now many commercially available and therapeutically effective ECM products for replacement of connective tissues such as skin, body wall and tendon.  The relative success of the commercial sector active in the natural ECM approach validates the scientific tenants, the feasibility of regulatory (FDA) approval, the viability of commercialization of this therapeutic approach, and “consumer” (physician and patient) acceptance.  However complex tissues and whole organs present unique challenges that current scientific methodologies cannot address - thus the need for the center that can drive the science and technology forward, serve as a test bed for new approaches, and serve as an intellectual and physical reservoir for state of the art techniques that are available to all interested parties.