RRC ID 77025
Author Zeng J, Tang SY, Toh LL, Wang S.
Title Generation of "Off-the-Shelf" Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells.
Journal Stem Cell Reports
Abstract Current donor cell-dependent strategies can only produce limited "made-to-order" therapeutic natural killer (NK) cells for limited patients. To provide unlimited "off-the-shelf" NK cells that serve many recipients, we designed and demonstrated a holistic manufacturing scheme to mass-produce NK cells from induced pluripotent stem cells (iPSCs). Starting with a highly accessible human cell source, peripheral blood cells (PBCs), we derived a good manufacturing practice-compatible iPSC source, PBC-derived iPSCs (PBC-iPSCs) for this purpose. Through our original protocol that excludes CD34+ cell enrichment and spin embryoid body formation, high-purity functional and expandable NK cells were generated from PBC-iPSCs. Above all, most of these NK cells expressed no killer cell immunoglobulin-like receptors (KIRs), which renders them unrestricted by recipients' human leukocyte antigen genotypes. Hence, we have established a practical "from blood cell to stem cells and back with less (less KIRs)" strategy to generate abundant "universal" NK cells from PBC-iPSCs for a wide range of patients.
Volume 9(6)
Pages 1796-1812
Published 2017-12-12
DOI 10.1016/j.stemcr.2017.10.020
PII S2213-6711(17)30475-7
PMID 29173894
PMC PMC5785702
MeSH Cell Culture Techniques / methods* Cell Differentiation / genetics* Cell Proliferation / genetics Embryoid Bodies / cytology Gene Expression Regulation, Developmental / genetics Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism Killer Cells, Natural / cytology* Killer Cells, Natural / metabolism Peripheral Blood Stem Cells / cytology Peripheral Blood Stem Cells / metabolism Receptors, KIR / genetics
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Human and Animal Cells OP9/DLL1