An Experimental Study Comparing the Expansion of Peripheral Blood Natural Killer (NK) Cells Cultured with Artificial Antigen-Presenting Cells, in the Presence or Absence of Bone Marrow Mesenchymal Stem Cells (MSCs)

Mol Biotechnol. 2020 May;62(5):306-315. doi: 10.1007/s12033-020-00250-2.

Abstract

NK cells have been seen as potential agents in adoptive immunotherapy for cancer. The main challenge for the success of this approach is to obtain a great quantity of activated NK cells for adoptive transfer. The present study had aimed to evaluate the effect of a feeder layer of irradiated MSCs in the in vitro expansion of NK cells. MSCs were obtained from the bone marrow (BM) cells remaining in the bag and filter used in the transplantation of hematopoietic stem cells. NK cells were obtained from peripheral blood (PB) of healthy volunteers. NK expansion and activation were stimulated by culture with artificial antigen-presenting cells (aAPCs) and IL-2, in the presence or absence of BM-MSCs. NK cell proliferation, phenotypic expression and cytotoxic activity were evaluated. Both culture conditions showed high NK purity with predominance of NK CD56brightCD16+ subset post expansion. However, cultures without the presence of MSCs showed higher NK proliferation, expression of activation markers (CD16 and NKG2D) and related cytotoxic activity. In this experimental study, the presence of a feeder layer of irradiated BM-MSCs interfered negatively in the expansion of PB-NKs, limiting their growth and activation. Further investigation is needed to understand the mechanisms of NK-MSC interaction and its implications.

Keywords: Immunotherapy; Mesenchymal stem cells; Natural killer cell expansion.

Publication types

  • Comparative Study

MeSH terms

  • Antigen-Presenting Cells / cytology*
  • Antigen-Presenting Cells / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation
  • Healthy Volunteers
  • Humans
  • Interleukin-2 / metabolism
  • K562 Cells
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Leukocytes, Mononuclear / cytology*
  • Leukocytes, Mononuclear / immunology
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Receptors, IgG / metabolism

Substances

  • FCGR3B protein, human
  • GPI-Linked Proteins
  • IL2 protein, human
  • Interleukin-2
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, IgG