Optimizing Recellularization of Whole Decellularized Heart Extracellular MatrixMatthew J. Robertson1,2, Jessica L. Dries-Devlin3, Stefan M. Kren1, Jana S. Burchfield4, Doris A. Taylor1,4,5*

Mary Kate Mehegan and Caroline CummingsAnimal Biotechnology October 17, 2014

Heart Disease● About 600,000 people die of heart disease in the

United States every year–that’s 1 in every 4 deaths.

● Coronary heart disease alone costs the United States $108.9 billion each year. This total includes the cost of health care services, medications, and lost productivity.

● Heart disease is the leading cause of death for people of most racial/ethnic groups in the United States, including African Americans, Hispanics, and whites. For Asian Americans or Pacific Islanders and American Indians or Alaska Natives, heart disease is second only to cancer.

http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_disease.htm

Recellularization - Bypassing the Transplant Compatibility Problem

http://www.nature.com/news/tissue-engineering-how-to-build-a-heart-1.13327

The Problem - Thrombosis, Poor Perfusion and Poor Contractility.

Thrombosis: The formation or presence of a blood clot in a blood vessel. The vessel may be any vein or artery as, for example, in a deep vein thrombosis or a coronary (artery) thrombosis.

Perfusion: The process of a body delivering blood to a capillary bed in its biological tissue.

Contractility: Previous models have had difficulty with ventricular contractility, endothelial cells must be delivered in a manner that appropriately localizes them to the vascular conduit surfaces and the ventricular cavity, not to the parenchyma of the scaffold.

How Can Thrombogenicity Be Reduced and Both Perfusion and Contractility Be Increased?● By re-endothelializing the perfusion-decellularized

acellular scaffold with functional endothelial cells, which reduces the thrombogenicity of scaffold.

● Re-endothelialization also improves contractile function of constructs that have been re-cellularized.

● These re-endothelialization studies are a first step toward generating an engineered functional arterial and venous vasculature that can be used to create transplantable, viable tissues and organs.

Would anyone like to state the overarching

question?

What about the hypothesis?

Overarching Question:Can the re-lining of vascular conduits of a decellularized rat heart with

rat aortic endothelial cells (RAECs) create a less thrombogenic scaffold, and improve recellularized-left ventricular contractility?

It is hypothesized that the re-lining of vascular conduits of a decellularized rat heart with rat aortic endothelial cells (RAECs) will

reduce thrombogenicity and improve both perfusion and recellularized-left ventricular contractility in a cadaveric heart recellularization model.

Aim 1: Determine which strategy for re-endothelialization leads to the most cell growth and distribution.

Aim 2: Determine if there is a correlation between cell delivery technique and the types of vessels re-lined with RAECs.

Aim 3: Determine if aortic retrograde perfusion is sufficient in maintaining cell survival throughout re-endothelialization.

Limitations

● Different strategies were used to re-endothelialize the scaffold to find optimal strategy (BA+IVC), yet continue to use BA (4x10^7) and BA+IVC.

● Some figures only display BA data.● The aortic re-endothelialization was not tested with 4.0x10^7

cells.● Transplanted hearts were only kept in rats for 7 days after re-

endothelialization.

Conclusion

● Re-endothelialization of a whole heart scaffold is optimal when cells are delivered through both venous and arterial coronary vessels.○ BA+IVC is optimal

● Re-endothelialization reduces scaffold thrombogenicity and enhances the function of the recellularized left ventricle.○ Thrombogenicity decreased○ Contractility increased

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