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Jan 15, 2014 (Vol. 34, No. 2)

Progress in Stem Cell Pluripotency

From our January 15 issue: Translational applications of pluripotency are gaining momentum, despite developmental, regulatory, and advocacy challenges.

  • The stem cell world finds itself at a critical juncture as the new year begins. That’s the view of Paul Knoepfler, Ph.D., associate professor at the UC Davis School of Medicine. Last month he moderated one of the sessions at the Genetics Policy Institute’s“World Stem Cell Summit.”

    “The field has been buoyed by building momentum for both transformative basic science discoveries and clinical translation of stem cells,” he noted. Yet, it’s also faced with serious challenges, including stem cell tourism, regulatory compliance, and physician training, according to Dr. Knoepfler.

    Pluripotent stem cells maintained at their most basic, dedifferentiated state, retain the capability to develop into the three main cell types—endoderm, mesoderm, or ectoderm-—and from there to each of the cell types that comprise the human body, including blood, muscle, and skin cells, or neurons, for example.

    The potential for producing targeted cell therapies from stem cells to treat disease and repair or regenerate tissues and organs defines the future trajectory of truly personalized medicine. Whether these therapies will be autologous or allogeneic, and whether they derive from embryonic stem cells (ESC) obtained from a blastocyst or from therapeutic cloning using somatic cell nuclear transfer, or derive from genetically reprogrammed adult cells to become induced pluripotent stem cells (iPSC), will likely depend on progress achieved in the next few years.

    An important challenge is to optimize the purity, definition, safety, ease of production, and cost efficiency of manufacturing therapies that fill unmet medical needs and offer cures and appreciable improvement in patient outcomes and quality of life.

  • Key Action Items

    Click Image To Enlarge +
    An immunolabeled cardiomyocyte (CM) imaged by scientists at the University of Wisconsin. The CM was derived from induced pluripotent stem cells (iPSCs) and labeled with an antibody to alpha-actinin (green), myosin light chain 2a (red), and DAPI (blue) for the nucleus. This labeling demonstrates the formation of myofilament proteins with a striated pattern in iPSC-CMs.

    In an article in World Stem Cell Report 2013, Dr. Knoepfler identified several key action items for the stem cell field in 2014. These are important because they relate not only to the field of pluripotent stem cells, but also to adult stem cell-based research and development. They include the need to train a new generation of stem cell clinicians, balance advocacy for responsible reforms at the FDA with the need to work with the agency, and monitor and raise awareness of noncompliant stem cell interventions no longer only available outside the U.S. but more recently proliferating at stem cell clinics across the U.S. He also put out the call to leverage social media to educate the public about stem cells and obtain funding for stem-cell-related research.

    The advantages of pluripotency can be exploited to produce a targeted population of cells for transplantation, genetic manipulation, delivery of a therapeutic agent, or regeneration of an organ. Stem cell lines are valuable research tools for studying cell biology, embryogenesis and developmental biology, and are proving increasingly useful in drug discovery and development for producing cell-based models of disease and for preclinical toxicology studies.

    Pluripotency can have a dark side as well, and when pluripotency control mechanisms go awry due to genomic or epigenomic changes, cell immortality and tumorigenicity may result.

    Timothy Kamp, M.D., Ph.D., professor and co-director, Stem Cell and Regenerative Medicine Center at the University of Wisconsin, Madison, presented his group’s latest work differentiating human pluripotent stem cells to create spontaneously contracting cardiomyocytes for cell therapy to repair cardiac muscle damaged as a result of ischemia (myocardial infarction), cardiomyopathies, certain arrhythmias, or valvular disease, for example.

    The paradigm he described for producing iPSC involves reprogramming skin or blood cells, expanding and cryopreserving the pluripotent stem cells to create an iPSC bank, and then using those cells to make relevant cellular products for cardiac repair or a tissue engineered cardiac patch. Dr. Kamp’s group has demonstrated proof-of-principle in mice that ESC can induce regeneration of cardiomyocytes in infarcted heart muscle. iPSC technology is “rapidly evolving,” said Dr. Kamp, as he demonstrated their progress toward growing human iPS-engineered cardiac tissue in the lab as a 3-dimensional model of functional human myocardium.

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