High-throughput proliferation and activation of NK-92MI cell spheroids via a homemade one-step closed bioreactor in pseudostatic cultures for immunocellular therapy
Journal
Journal of Biological Engineering
Journal Volume
18
Journal Issue
1
Start Page
65
ISSN
1754-1611
Date Issued
2024-12
Author(s)
Jhih-Ni Lin
Che-Yung Kuan
Chia-Ting Chang
Zhi-Yu Chen
Jason Lin
Yu-Ying Lin
I.-Hsuan Yang
DOI
10.1186/s13036-024-00461-0
Abstract
The NK-92MI cell line has displayed significant promise in clinical trials for cancer treatment. However, challenges persist in obtaining sufficient cell quantities and achieving optimal cytotoxicity. The proliferation of natural killer (NK) cells involves the formation of cell aggregates, but excessively large aggregates can impede nutrient and waste transport, leading to reduced cell survival rates. In this study, a custom bioreactor was designed to mimic pseudostatic culture conditions by integrating brief mechanical rotation during a 6-h static culture period. This method aimed to achieve an optimal aggregate size while improving cell viability. The findings revealed a 144-fold expansion of 3D NK-92MI cell aggregates, reaching an ideal size of 80–150 µm, significantly increasing both cell proliferation and survival rates. After 14 days of culture, the NK-92MI cells maintained their phenotype during the subsequent phase of cell activation. Moreover, these cells presented elevated levels of IFN-γ expression after IL-18 activation, resulting in enhanced NK cell-mediated cytotoxicity against K562 cells. This innovative strategy, which uses a closed suspension-based culture system, presents a promising approach for improving cell expansion and activation techniques in immunocellular therapy.
Subjects
Custom-made closed bioreactor
Immune cell activation
Immunocellular therapy
NK cell expansion
Pseudostatic culture
Publisher
Springer Science and Business Media LLC
Type
journal article