11 August 2022

Is it possible to scale up cell production while maintaining high-quality?

Yes it is- large scale cell culturing of pluripotent stem cells in bioreactors with Biolaminin® coated micro- and macro beads has proved to meet clinical needs – both in quantity and quality

Biolaminin 521 coated microcarrier systems can easily be scaled up in dynamic large-scale culture systems such as stirred bioreactors due to their 3D suspended nature. This system leads to high volumetric cell yield which is achieved due to better oxygenation, better metabolite mass transport, and limited microenvironment toxicity. In comparison to monolayer culture, this system allows cost-effective, GMP-compliant production of large amounts of clinical-grade hPSC with consistent and predictable characteristics to achieve the needs in developing cellular therapy.

Defined and scalable bioprocessing platform to produce hPSCs with Biolaminin 521-based microcarrier system

A bioreactor system with Biolaminin-521 coated microcarriers was reported to offer a GMP-compatible and scalable bioprocessing platform to produce human embryonic stem cells (hESCs) with the quantity and quality compliant for clinical applications (Lam et al. 2015). BioLaminin 521 coated microcarriers efficiently supported hESC attachment, spreading, and growth in agitated conditions, without the need for additional positive charges. Importantly, the cultured cells-maintained pluripotency for more than 10 passages and retained normal karyotype. The cells were able to differentiate into lineages of all three germ layers and then specifically to cardiomyocytes.

A) HES-3 embryonic stem cell density on coated polystyrene microcarriers (MC) after 7 days of culture. Images show representative hESC/MC aggregates, scale bars 200 μm. Modified from Lamet al. 2014 Stem Cells and Development, fig. 4 (CC BY 4.0). PLL = poly-L-lysine, LM = laminin-111.

Scaling up clinically adaptable red blood cell production from hPSCs using Biolaminin 521-coated microcarriers

A chemically defined method, utilizing Biolaminin 521 and microcarrier-based suspension culture, was applied to scale up red blood cell (RBC) production (Sivalingam et al. 2018, Sivalingam et al. 2020). The improved cell survival and the better-quality process resulted in significant improvement in hematopoietic precursor expansion and RBC yield compared to a conventional embryoid body-based method.

Biolaminin 521 as a superior hollow fiber coating substrate for large-scale expansion of hiPSCs in a closed cell expansion system

Quantum Cell Expansion System (QES) coated with Biolaminin 521 was shown to provide the necessary environment for exponential induced pluripotent stem cell (iPSC) growth (Mesquita et al. 2019). Exponential iPSC growth was not observed when vitronectin coating was used in the QES, even though media consumption was the same under both conditions. This indicates that the coating has an important effect on the proliferation rate of the cells.

A) Significantly improved cell proliferation with LN521 coating.

B) The cells-maintained pluripotency, karyotype, and differentiation capability to all three germ layers. A subset of the measured pluripotency markers is shown in the figure. From Mesquita et al. 2019 Stem Cells International, figs. 2 and 3 (CC BY 4.0).

Developing megakaryocyte production from stem cells using Biolaminin 521- coated microcarriers for platelet transfusion in bleeding disorders

The Biolaminin 521 coated microcarrier beads in stirred bioreactors were also shown to increase megakaryocyte production per iPSC by up to 10-fold (Eicke et al. 2018). Megakaryocytes are the precursors of platelets and they can be used for platelet production, as well as a source for platelet-derived growth factors. Megakaryocytes obtained with this system showed typical features of mature cells and were able to produce platelets in vitro and in vivo. The possibility to use freshly produced platelets in large numbers will facilitate the development of megakaryocyte-based therapeutic strategies.

A) Using Biolaminin 521-coated non-porous polystyrene microcarriers (cell-MC), 30 megakaryocytes (MKs) per input iPSC could be produced, compared to only 4 MKs in cellaggregate suspension culture (cell-OA). B) Pro-platelet cells formed at a high percentage, indicating functional MK cells. From Eicke et al. 2018 Scientific Reports, figs. 3, 4 (CC BY 4.0)
  • Large-scale cell production – read more about how Biolaminin improves large-scale cell manufacturing processes
  • See all Biolaminin isoforms – supporting different cell types in the body
  • Biolaminin 521 LN – natural laminin that facilitate self-renewal of human ES and iPS cells in a chemically defined, feeder-free and animal origin-free stem cell culture system

Bio-Connect Life Sciences supplies all BioLamina products in the Benelux. If you have any questions, please contact the helpdesk.

Is it possible to scale up cell production while maintaining high-quality?

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