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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Stem cell combination augments cardiac repair in rat models

Scientists have provided early evidence for the use of a combination of stem cell-derived cardiac cells in augmenting damaged heart in rat models.

Cardiovascular disease is the leading cause of death worldwide. Cardiac regeneration could serve as a powerful strategy for treating severe heart failure, however, cardiomyocytes (heart muscle cells) have poor regenerative capacity. Currently, there are several emerging strategies for cardiac regeneration including cell transplantation therapy using newly generated cardiomyocytes from exogenous sources, such as pluripotent stem cells.

While substantial progress has been made in stem cell transplantation therapy for cardiac regeneration, challenges remain for clinical translation. One of the major challenges is the limited survival of stem cells after being transplanted into the heart, making it largely ineffective.

In the present study, a collaborative research conducted at the University of Cambridge and the University of Washington developed a strategy to help the newly generated cardiomyocytes live longer in the transplanted heart.

A combination of cells derived from human stem cells: cardiomycoytes to regenerate the damaged tissue, and epicardial cells from the outer part of the heart wall to help the muscle cells live longer, was tested in damaged heart in rat models.

The combination of human embryonic stem cell-derived heart cells was first tested in 3D models of human heart tissue. They observed that the epicardial cells promoted the growth and maturation of cardiomyocytes and improved their ability to contract.

Co-transplantation of stem cell-derived epicardial cells and cardiomyocytes doubled graft cardiomyocyte proliferation rates in vivo compared with using these cells alone. The researchers also observed an improvement in “systolic functioning,” which is the ability of the left ventricle of the heart to contract normally.

Taken together, these findings support the use of stem cell combination therapy in repairing damaged heart. The ability of epicardial cells to enhance cardiac graft size and function makes them a promising adjuvant source for cardiac repair. The study opens the door for additional studies and testing the strategy in higher animal models before clinical translation. The study was published in the journal Nature Biotechnology.

Sir Nilesh Samani, Medical Director at the British Heart Foundation which partially funds the study commented: “When it comes to mending broken hearts, stem cells haven’t yet really lived up to their early promise. We hope that this latest research represents the turning of the tide in the use of these remarkable cells.”

Source: Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration. Bargehr J et al., Nature Biotechnology, August 2019. DOI

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