Natural Killer Cell

Natural Killer (NK) cells originate and differentiate from hematopoietic stem cells through various signalling pathways involving cytokines and interleukins. These cells arise from CD34+ lymphoid progenitors and comprise 10-15% of all lymphocytes in human peripheral blood. Once completely differentiated, NK cells lack B (CD19-) and T(CD3-) lymphocyte markers and carry their unique CD56+ status instead. The two maturate variants of NK cells are CD56dim and CD56bright, which exert cytotoxicity through release of toxic chemicals and cytokine secretion, respectively. NK Cells express features of innate immune responses, and respond to all molecules that appear to be foreign to the body.

The most standard and utilized source of NK cells is directly from the peripheral blood of a donor through leukapheresis: a technique where immune cells are separated from red blood cells. Generally, the number of NK cells collected in the peripheral blood mononuclear cell (PBMC) is too low for sufficient potency, and ex vivo expansion is performed. Expansion involves the use of feeder cell line systems or bioreactors to enhance the number of NK cells with desired cytotoxicity. These cells are also purified using cell-separation systems and processing.

Other techniques involve using umbilical cord blood (UCB) directly; these NK cells have heterogeneous CD56 expression but are considered suitable for immunotherapy. It is also possible to culture UCB CD34+ hematopoietic stem cells (HSCs) under stimulation of IL-2, IL-15, and stem cell factor (SCF) in a system to develop NK cells.

Induced pluripotent stem cells (iPSCs) and human embryonic stem cells (HESCs) are also used to generate NK cells through a two-step culture method resulting in CD34+ cells.