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Faculty Focus: New publications from Dr. Ren-Ke Li

Jiao Li, Shu-Hong Li, Jun Wu, Richard D. Weisel, Alina Yao, William L. Stanford, Shi-Ming Liu, Ren-Ke Li. Young Bone Marrow Sca-1 Cells Rejuvenate the Aged Heart by Promoting Epithelial-to-Mesenchymal Transition.  Theranostics 2018; 8(7): 1766-1781.

Heart failure is an important cardiovascular clinical problem. Despite advances in clinical care, congestive heart failure remains a major worldwide medical problem with significant morbidity and mortality, especially in the aged population.

We have developed a new technology to improve tissue repair or regeneration in aged patients (rejuvenation). This method is based on the theory that the bone marrow is a reservoir of stem cells which contribute to tissue repair after injury. Using an animal model, we replaced the bone marrow of old individuals with bone marrow cells from young donors and successfully rejuvenated the aged recipient bone marrow with these young stem cells. Next we demonstrated that the young stem cells were mobilized to many organs including the heart and organ specific resident stem cells. These young stem cells were able to alter the heart microenvironment. Then, following injury to the aged heart, these cardiac resident young stem cells were able to secrete growth factors to stimulate the proliferation of aged cardiac cells, which then transformed from epithelial cells into mesenchymal cells. This process repopulated mesenchymal cells in the heart which enhanced tissue repair and restored heart function. All these activities were initiated by resident young stem cells in the aged heart resulting in repair after injury and prevented heart failure. The mechanistic analysis in current publication demonstrated that “rejuvenation” of aged heart was possible. These novel results suggests that we are able to develop the “next generation” of cell therapy for restoration of heart function of aged patients.

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Sheng He, Huifang Song, Jun Wu, Shu-Hong Li, Richard D. Weisel , Hsing-Wen  Sung, Jianding Li, Ren-Ke Li. Preservation of conductive propagation after surgical repair of cardiac defects with a bio-engineered conductive patch. J Heart Lung Transplant. Online: 2017 Dec 20.

Congenital or acquired cardiac defects which significantly affect cardiac function can contribute to congestive heart failure. Advanced surgical procedures have made it possible to correct or repair most cardiac defects using stable surgical materials. Although surgical procedures are successful, many patients, especially those patients with congenital cardiac defect, may continue to have some cardiac dysfunction due to the inability of the cardiac grafts to conduct electrical activity in the heart.

In this publication we reported that we have created a new cardiac graft using conductive biomaterials. The new material has two major biological functions: 1) the heart cells can grow in the material and are able to continue to contract (the material is biocompatible); and 2) the novel biomaterial is bio-conductive because the heart cells grown on the conductive biomaterial have synchronous contraction. To investigate the biological function of this new conductive biomaterial, we then created a heart defect model using adult rats which was repaired with the conductive grafts. At 4 weeks after the ventricular defect repair, we observed properly conducting  electrical signals across the cardiac patch. The new conductive cardiac graft enhanced the transmission of electrical signals that control the pumping of the heart. The conductive biomaterial restored the normal pattern of coordinated heart contraction after surgical correction of the heart defect. The new material is unique because it facilitates electrical conduction and keeps the heart beating synchronously.

These research results may provide a new treatment for cardiac patients that is possible more effective than current therapies. This new approach could allow patients to have better cardiac function and return to a normal lifestyle.

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Professor, Department of Surgery, Division of Cardiovascular Surgery, University of Toronto

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