Stem-cell-based therapy and lessons from the heart

Abstract

The potential usefulness of human embryonic stem cells for therapy derives from their ability to form any cell in the body. This potential has been used to justify intensive research despite some ethical concerns. In parallel, scientists have searched for adult stem cells that can be used as an alternative to embryonic cells, and, for the heart at least, these efforts have led to promising results. However, most adult cardiomyocytes are unable to divide and form new cardiomyocytes and would therefore be unable to replace those lost as a result of disease. Basic questions--for example, whether cardiomyocyte replacement or alternatives, such as providing the damaged heart with new blood vessels or growth factors to activate resident stem cells, are the best approach--remain to be fully addressed. Despite this, preclinical studies on cardiomyocyte transplantation in animals and the first clinical trials with adult stem cells have recently been published with mixed results.

Constraining the Pluripotent Fate of Human Embryonic Stem Cells for Tissue Engineering and Cell Therapy – The Turning Point of Cell-Based Regenerative Medicine

“…So far, the lack of a clinically-suitable human cardiomyocyte source with adequate myocardium regenerative potential has been the major setback in regenerating the damaged human heart, either by endogenous cells or by cell-based transplantation or cardiac tissue engineering [3,12,13,78,103,104]. In the adult heart, the mature contracting cardiac muscle cells, known as cardiomyocytes, are terminally differentiated and unable to regenerate.…”

“…Damaged or diseased cardiomyocytes are removed largely by macrophages and replaced by scar tissue. Although cell populations expressing stem/progenitor cell markers have been identified in postnatal hearts, the minuscule quantities and growing evidences indicating that they are not genuine heart cells have caused skepticism if they can potentially be harnessed for cardiac repair [78,105–110]. There is no evidence that stem/precursor/progenitor cells derived from other sources, such as bone marrow, cord blood, umbilical cord, fat tissue, or placenta, are able to give rise to the contractile heart muscle cells following transplantation into the heart [3,78,104].…”

“…Current cell delivery methods to the damaged heart, by injection of cells either directly into the infarcted region or via the coronary circulation, are inefficient [78,103,104]. In addition, arrhythmogenesis is a potential risk in cell-based cardiac repair [78,103,104].…”

“…In addition, arrhythmogenesis is a potential risk in cell-based cardiac repair [78,103,104]. So far, the need to regenerate or repair the damaged heart muscle (myocardium) has not been met by adult stem cell therapy, either endogenous or via cell delivery [78,103,104].…”

Patents on Technologies of Human Tissue and Organ Regeneration from Pluripotent Human Embryonic Stem Cells

“…In the remaining patients who survive their initial acute event, the damage sustained by the heart may eventually develop into heart failure, with an estimated median survival of 1.7 years in men and 3.2 years in women [126, 127]. To date, the lack of a suitable human cardiac cell source has been the major setback for regenerating the human myocardium, either by cell-based transplantation or by cardiac tissue engineering [126, 127]. Cardiomyocytes become terminally-differentiated soon after birth and lose their ability to proliferate.…”