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. 2020 Mar 28;7(2):31.
doi: 10.3390/bioengineering7020031.

Challenges and Solutions for Commercial Scale Manufacturing of Allogeneic Pluripotent Stem Cell Products

Brian Lee  1 , Breanna S Borys  2 , Michael S Kallos  2 , Carlos A V Rodrigues  3 , Teresa P Silva  3 , Joaquim M S Cabral  3
Affiliations

Challenges and Solutions for Commercial Scale Manufacturing of Allogeneic Pluripotent Stem Cell Products

Brian Lee et al. Bioengineering (Basel). .

Abstract

Allogeneic cell therapy products, such as therapeutic cells derived from pluripotent stem cells (PSCs), have amazing potential to treat a wide variety of diseases and vast numbers of patients globally. However, there are various challenges related to the manufacturing of PSCs in large enough quantities to meet commercial needs. This manuscript addresses the challenges for the process development of PSCs production in a bioreactor, and also presents a scalable bioreactor technology that can be a possible solution to remove the bottleneck for the large-scale manufacturing of high-quality therapeutic cells derived from PSCs.

Keywords: U-shaped vessel; Vertical-Wheel; allogeneic cell therapy; cell aggregate; computational fluid dynamics; differentiation; expansion; homogeneous hydrodynamic environment; human embryonic stem cell; induced pluripotent stem cell; scalable manufacturing; scale up; shear stress; single-use bioreactor; turbulent energy dissipation rates.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Computational fluid dynamics (CFD) analyses of shear stress on the surface of vertical-wheel impeller and range of turbulent energy dissipation rates in U-shaped vessel.
Figure 2
Figure 2
(A) Projected distribution of cell aggregate sizes in Vertical-Wheel bioreactor (homogeneous) vs. horizontally stirred bioreactor (non-homogeneous) hydrodynamic environments. (B) inverse correlation between average pluripotent stem cells (PSC) aggregate diameter and agitation rate in Vertical-Wheel bioreactors.
Figure 2
Figure 2
(A) Projected distribution of cell aggregate sizes in Vertical-Wheel bioreactor (homogeneous) vs. horizontally stirred bioreactor (non-homogeneous) hydrodynamic environments. (B) inverse correlation between average pluripotent stem cells (PSC) aggregate diameter and agitation rate in Vertical-Wheel bioreactors.
Figure 3
Figure 3
(A) Inverse correlation between average iPSC aggregate diameter and agitation rates in Vertical-Wheel bioreactor (0.1 L Scale). (B) Comparison of iPSC aggregate diameters and morphology with different agitation rates in Vertical-Wheel bioreactor vs. horizontal-blade spinner (0.1 L scale). Scale bar (200 µm).
Figure 4
Figure 4
Directed differentiation of human iPSCs into cerebellar organoids in 0.1 L scale Vertical-Wheel bioreactor. Scale bar (100 µm).
Figure 5
Figure 5
Successful Serial Passaging of iPSCs in 0.1 L Scale Vertical-Wheel Bioreactors.
See this image and copyright information in PMC

References

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