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Large-scale production of megakaryocytes in microcarrier-supported stirred suspension bioreactors

Dorothee Eicke1,2, Anja Baigger1, Kai Schulze3

  • 1Institute for Transfusion Medicine, Hannover Medical School, Hannover, 30625, Germany.

Scientific Reports
|July 7, 2018
PubMed

Insights

This study developed a scalable, xeno-free bioreactor system for producing megakaryocytes (MKs) from induced pluripotent stem cells. This method efficiently generates functional MKs for platelet production and cell therapies.

Area of Science:

  • Stem cell biology
  • Biotechnology
  • Hematology

Background:

  • Megakaryocytes (MKs) are crucial for platelet production.
  • Induced pluripotent stem cells (iPSCs) offer a renewable source for MK generation.
  • Existing methods for in vitro MK production face challenges in scalability and safety.

Purpose of the Study:

  • To develop an effective, xeno-free, and scalable system for high-yield MK production.
  • To evaluate microcarrier-assisted stirred bioreactors for enhancing MK yields.
  • To assess the functionality and safety of bioreactor-generated MKs.

Main Methods:

  • Utilized induced pluripotent stem cells (iPSCs) as the starting material.
  • Employed microcarrier beads in stirred bioreactors for MK cultivation.
  • Investigated laminin-coated microcarriers to optimize MK production.
  • Irradiated generated MKs to enhance safety for therapeutic applications.

Main Results:

  • Achieved production of 18.7 × 10^7 MKs per 50 ml medium.
  • Laminin-coated microcarriers increased MK production from iPSCs up to 10-fold.
  • Generated MKs exhibited mature characteristics and produced functional platelets in vitro and in vivo.
  • Irradiation did not impair the proplatelet and platelet formation capacity of MKs.

Conclusions:

  • Microcarrier-assisted stirred bioreactors provide a scalable and effective platform for xeno-free MK production.
  • In vitro generated MKs are a promising alternative to donor platelets.
  • These findings support the development of novel MK-based cell therapies.

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