Unit 10.2 - Mass Production of Pluripotent Stem Cells and Derivatives

Objectives

We aim to

  • Establish human pluripotent stem cell (hPSC) culture (including hiPSCs and hESCs) in clinical scale and grade.
  • Establish efficient cardiomyogenic differentiation of hPSCs and provide. cardiomyocytes for tissue engineering and heart repair in pre-clinical animal model.
  • Perform process development for hPSC production and differentiation in controlled bioreactor.
  • Achieve in vitro modeling of congenital cardiomyopathie.
  • Achieve process up-scaling to 1 Liter scale in stirred bioreactors.

Research Focus

Our research resulted in recent milestone papers on the defined, single cell inoculated cultivation of human pluripotent stem cells (hPSC, including hESCs and hiPSCs) as “cells only” aggregates in suspension culture, independent of micro carriers or other extracellular matrices. This technique, for the first time, enables straightforward up-scaling of hPSC culture in, fully controllable stirred-tank bioreactors providing the required “raw material” for the mass production of any differentiated human PSC-derived progenies. Independent research allowed the generation of pure human hPSC-derived cardiomyocytes (CMs) in chemically defined, clinically compliant culture media in suspension culture. We are currently working on combining the hPSC suspension culture process with our CMs differentiation protocol in controlled bioreactors to develop clinically relevant conditions for CMs production. Cells will be provided “on-demand” in frame of REBIRTH-2 collaborative projects, particularly for cardiac tissue engineering and in vitro modelling of cardiomyopathies.

Achievements

  • Robust hPSC expansion and maintenance of pluripotency when cultured in suspension as “cell only” aggregates in 100 ml scale stirred bioreactors in defined media
  • Efficient cardiomyogenic differentiation of hPSCs in stirred bioreactors achieving 80-90% cardiomyocyte purity in chemically defined media

Collaborations (selection)

Grants (selection)

  • StemBANCC: Large-scale, 5 year academic-industry partnership. Aims: hiPSC lines for in vitro modeling of chronic diseases and drug testing.

Extra

Established industrial collaborations on process development & reactor technology with:

  • STEMCELL Technologies (Vancouver, Canada)
  • DASGIP / Eppendorf (Jühlich / Hamburg, Germany)

Equipment and Service Facilities

[Please find a list of all available equipment here]

Staff

Zweigerdt, Robert Dr. Zweigerdt.Robert(at)mh-hannover.de
Olmer, Ruth Dr. Olmer.Ruth(at)mh-hannover.de
Schwanke, Kristin Dr. Schwanke.Kristin(at)mh-hannover.de
Hartung, Susann Hartung.Susann(at)mh-hannover.de
Jara-Avaca, Monica Jara-Avaca.Monica(at)mh-hannover.de
Kempf, Henning Kempf.Henning(at)mh-hannover.de
Franke, Annika Franke.Annika(at)mh-hannover.de
Zink, Annika annika-zink(at)t-online.de
Perk, Jonas Perk.Jonas(at)mh-hannover.de
Robles Diaz, Diana r.diaz.diana(at)gmail.com