Defective flow space limits the scaling up of turbulence bioreactors for platelet generation

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Abstract
To complement donor-dependent platelets supplies, we previously developed an ex vivo manufacturing system using induced pluripotent stem cell (iPSC)-derived expandable immortalized megakaryocyte progenitor cell lines (imMKCLs), and a turbulent flow bioreactor to generate iPSC-derived platelets products (iPSC-PLTs). However, the tank size of the bioreactor was limited to 10 L. Here we examined the feasibility of scaling up to 50 L with reciprocal motion by two impellers. Under optimized turbulence parameters corresponding to 10 L bioreactor, 50 L bioreactor elicited iPSC-PLTs with intact in vivo hemostatic function but with less production efficiency. This insufficiency was caused by increased defective turbulent flow space. A computer simulation proposed that designing 50 L turbulent flow bioreactor with three impellers or a new bioreactor with a modified rotating impeller and unique structure reduces this space. These findings indicate that large-scale iPSC-PLTs manufacturing from cultured imMKCLs requires optimization of the tank structure in addition to optimal turbulent energy and shear stress.
Funding Information
  • Japan Agency for Medical Research and Development (JP20bm0704051, JP23bm1323001, JP23bm1323001)
  • MEXT | Japan Society for the Promotion of Science (KIBAN S, 21H05047, 23K18299, 22K18169)
  • the CiRA Foundation Fund Otsuka Pharmaceutical Co., Ltd. Megakaryon Corporation Satake Multimix Corporation
  • JST FOREST Program JPMJFR225K

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