Development of a scalable suspension culture for cardiac differentiation from human pluripotent stem cells

Stem Cell Research
Vincent C ChenLarry A Couture

Abstract

To meet the need of a large quantity of hPSC-derived cardiomyocytes (CM) for pre-clinical and clinical studies, a robust and scalable differentiation system for CM production is essential. With a human pluripotent stem cells (hPSC) aggregate suspension culture system we established previously, we developed a matrix-free, scalable, and GMP-compliant process for directing hPSC differentiation to CM in suspension culture by modulating Wnt pathways with small molecules. By optimizing critical process parameters including: cell aggregate size, small molecule concentrations, induction timing, and agitation rate, we were able to consistently differentiate hPSCs to >90% CM purity with an average yield of 1.5 to 2×10(9) CM/L at scales up to 1L spinner flasks. CM generated from the suspension culture displayed typical genetic, morphological, and electrophysiological cardiac cell characteristics. This suspension culture system allows seamless transition from hPSC expansion to CM differentiation in a continuous suspension culture. It not only provides a cost and labor effective scalable process for large scale CM production, but also provides a bioreactor prototype for automation of cell manufacturing, which will accelerate the advance of ...Continue Reading

References

Jul 9, 2005·Nature Biotechnology·Michael A Laflamme, Charles E Murry
Nov 24, 2005·Nature Reviews. Genetics·Margaret BuckinghamStéphane Zaffran
Dec 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Atsuhiko T NaitoIssei Komuro
Mar 28, 2007·Nature Reviews. Genetics·Patrick P L Tam, David A F Loebel
May 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shuichi UenoCharles E Murry
Jan 9, 2009·Nature Reviews. Molecular Cell Biology·Sebastian J Arnold, Elizabeth J Robertson
Sep 10, 2009·Tissue Engineering. Part C, Methods·Roman KrawetzDerrick E Rancourt
Mar 31, 2010·Nature Biotechnology·Debora SteinerBenjamin Reubinoff
Apr 7, 2010·Stem Cell Research·Harmeet SinghRobert Zweigerdt
May 1, 2010·Stem Cell Reviews and Reports·Michal AmitJoseph Itskovitz-Eldor
Mar 31, 2012·Stem Cell Research·Vincent C ChenLarry A Couture
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xiaojun LianSean P Palecek
Feb 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Reza ArdehaliIrving L Weissman
May 13, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Praveen ShuklaStephen T O'Rourke
Jun 16, 2014·Nature Methods·Paul W BurridgeJoseph C Wu

❮ Previous
Next ❯

Citations

Dec 15, 2015·Advanced Drug Delivery Reviews·Henning KempfRobert Zweigerdt
Mar 25, 2016·Nature Reviews. Cardiology·Ian Y ChenJoseph C Wu
Sep 18, 2016·Current Treatment Options in Cardiovascular Medicine·Hidetoshi Masumoto, Jun K Yamashita
Mar 16, 2017·The Journal of Physiology·Wolfram-Hubertus Zimmermann
Jun 7, 2018·Circulation. Genomic and Precision Medicine·Kiran MusunuruUNKNOWN American Heart Association Council on Functional Genomics and Translational Biology; Council on Cardiovascular Disease in th
Apr 7, 2017·Journal of Tissue Engineering and Regenerative Medicine·Chee Keong KwokFrank Edenhofer
Jul 4, 2020·Stem Cells Translational Medicine·Lila R Collins, Kelly A Shepard
Nov 28, 2017·Biotechnology and Bioengineering·Cláudia CorreiaMargarida Serra
Jan 1, 2019·Stem Cells International·Sushrut DakhoreKouichi Hasegawa
Jun 1, 2019·Stem Cells International·Teresa P SilvaTiago G Fernandes
Sep 22, 2020·Current Protocols in Stem Cell Biology·Duncan C MillerSebastian Diecke
May 30, 2019·Bioengineering·Minh Nguyen Tuyet Le, Kouichi Hasegawa
Feb 6, 2020·Nature Reviews. Cardiology·Elaheh KarbassiCharles E Murry
Mar 13, 2020·APL Bioengineering·Eileen L BradyKelly R Stevens
Jul 29, 2017·Current Cardiology Reports·Buntaro Fujita, Wolfram-Hubertus Zimmermann
May 12, 2017·Nature Protocols·Kaja BreckwoldtArne Hansen
Jun 23, 2019·Current Cardiology Reports·Shin Kadota, Yuji Shiba
Jun 21, 2020·Current Cardiology Reports·Arun Sharma
Aug 15, 2020·Frontiers in Bioengineering and Biotechnology·Bianca WilliamsSelen Cremaschi
Jun 24, 2018·Bioengineering·Cláudia C MirandaJoaquim M S Cabral
Jun 25, 2020·International Journal of Molecular Sciences·Elvira Immacolata ParrottaGiovanni Cuda
Aug 14, 2020·Bioengineering·Mariana A BrancoMaria Margarida Diogo
Nov 28, 2018·Communications Biology·Ngan F HuangJoseph C Wu
Oct 28, 2019·NPJ Science of Food·Luke A MacQueenKevin Kit Parker
Oct 25, 2020·Stem Cell Reviews and Reports·Pallavi PushpMukesh Kumar Gupta
Nov 17, 2020·Frontiers in Bioengineering and Biotechnology·Preeti AshokEmmanuel S Tzanakakis
Dec 2, 2020·Journal of Cardiovascular Translational Research·Ampadu O JacksonShiyin Long
Nov 19, 2020·Biotechnology and Bioengineering·Elena F JacobsonEmmanuel S Tzanakakis
Jun 10, 2018·Advanced Drug Delivery Reviews·Alexa WnorowskiJoseph C Wu
Apr 17, 2017·Biochemical and Biophysical Research Communications·Kunio HiranoHiroo Iwata

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Regeneration

Cardiac regeneration enables the repair of irreversibly damaged heart tissue using cutting-edge science, including stem cell and cell-free therapy. Discover the latest research on cardiac regeneration here.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.

Bioreactors (ASM)

Bioreactors are important devices or systems that utilize living cells or enzymes for a chemical process. These devices carefully control and monitor the environment factors such as pH, nutrients level, and temperature, which can affect the yield in a given process. Discover the latest research here.