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Updated: Apr 16, 2026

Generation of Natural Killer Cells from Human Expanded Potential Stem Cells
Published on: January 13, 2023
Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural
Mirelle J A J Huijskens1, Mateusz Walczak1, Subhashis Sarkar1
1Department of Internal Medicine, Division of Haematology, Maastricht University Medical Center, Maastricht, The Netherlands.
Background Aims:
Natural killer (NK) cell-based immunotherapy is a promising treatment for a variety of malignancies. However, generating sufficient cell numbers for therapy remains a challenge. To achieve this, optimization of protocols is required.
Methods:
Mature NK cells were expanded from peripheral blood mononuclear cells PBMCs in the presence of anti-CD3 monoclonal antibody and interleukin-2. Additionally, NK-cell progenitors were generated from CD34(+) hematopoietic stem cells or different T/NK-cell progenitor populations. Generated NK cells were extensively phenotyped, and functionality was determined by means of cytotoxicity assay.
Results:
Addition of ascorbic acid (AA) resulted in more proliferation of NK cells without influencing NK-cell functionality. In more detail, PBMC-derived NK cells expanded 2362-fold (median, range: 90-31,351) in the presence of AA and were capable of killing tumor cells under normoxia and hypoxia. Moreover, hematopoietic stem cell-derived progenitors appeared to mature faster in the presence of AA, which was also observed in the NK-cell differentiation from early T/NK-cell progenitors.
Conclusions:
Mature NK cells proliferate faster in the presence of phospho-L-AA, resulting in higher cell numbers with accurate functional capacity, which is required for adoptive immunotherapy.
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