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Priming Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation


DURHAM, N.C.  (
MAY 14, 2019)A study recently published in STEM CELLS shows a new method for accelerating human pluripotent stem cell-derived cardiomyocytes’ (hPSC-CMs) development. If a way can be found to overcome hPSC-CMs’ developmental immaturity, which leaves them functionally and structurally different from mature human cardiomyocytes, they can be powerful tools for disease modeling, drug development, basic research and new therapies. This study shows great promise in resolving this issue.

Other studies have focused on maturation strategies using a variety of interventions on differentiated hPSC-CMs. This one; however, investigated what would happen if early cardiac progenitor cells (CPCs) — a middle stage between stem cells and differentiated hPSC-CMs — were primed with polyinosinc-polycytidylic acid (pIC).

“This is a fundamentally different approach to promote maturation of hPSC-CMs by intervening at the progenitor stage,” said Timothy Kamp, M.D., Ph.D., Director of the Stem Cell and Regenerative Medicine Center at the University of Wisconsin-Madison and lead investigator on the study.

Dr. Kamp’s team differentiated CPCs from hPSCs using a monolayer protocol with defined small molecule Wnt pathway modulation. Then pIC was added as the CPCs began forming. The priming produced hPSC-CMs of increased size, greater contractility, faster electrical upstrokes, increased metabolism and more mature sarcomere structure and composition.

When the cells were tested by transplanting them into the kidney capsules of mice, “The primed CPCs showed more robust formation of hPSC-CMs grafts,” Dr. Kamp reported. “This gives us reason to believe that the modulation of CPCs with pIC accelerates cardiomyocyte maturation, and it could potentially enable future therapeutic uses.”

First author, Mitch Biermann, M.D., Ph.D., agreed and added, “We’re looking forward to testing pIC-primed CPCs in heart attack models. Using pIC priming should also improve the in vitro uses for mature hPSC-CMs such as studying disease mechanisms, drug responses and basic human cardiomyocyte biology.”

“Developing fully mature cells from pluripotent sources has been a major translational hurdle," said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. “The significant progress in maturing cardiomyocytes, reported in this manuscript, is highly important in moving the therapy closer to clinical application.”

The full article, “Epigenetic priming of human pluripotent stem cell-derived cardiac progenitor cells accelerates cardiomyocyte maturation,” can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3021.

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About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® (http://www.StemCells.com) is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST® (http://www.TheOncologist.com) is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® (http://www.StemCellsTM.com) is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

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