In vitro generation of dendritic cells derived from cryopreserved CD34+ cells mobilized into peripheral blood in lymphoma patients

Cytotherapy. 2000;2(2):95-104. doi: 10.1080/146532400539099.

Abstract

Background: Dendritic cells (DC) are APC that initiate primary T-cell dependent immune responses. They have been shown to be generated from CD34+ cells in BM, placental/umbilical cord blood (CB), and G-CSF mobilized peripheral blood CD34+ cells (PBSC). In recent clinical studies, DC were used as a vaccine for cancer patients and showed induction of their antitumor effects. Cryopreservation of CD34+ cells is important to extend the availability of cellular therapy with DC. However, little is known about the effect of cryopreservation on the functional maturation of DC.

Methods: PBSC harvested from lymphoma patients mobilized with G-CSF and undergoing leukapheresis were cryopreserved at -135 degrees C for 3 days. Freshly isolated or cryopreserved PBSC were cultured with GM-CSF/SCF/tumor necrosis factor-alpha (TNF-alpha). After 14 days of culture, DC were harvested, washed, and used for phenotypical and functional analysis.

Results: Cryopreserved PBSC, as well as freshly-isolated PBSC cultured for 14 days, gave rise to CD1a+ /CD4+ /CD11c+ /CD14low+ /CD25( -)/CD40+ / CD45RO+/CD80+/CD83+/CD86+/HLA-DR+ cells with dendritic morphology. DC derived from cryopreserved PBSC mobilized with G-CSF showed a similar endocytic capacity and chemotactic migratory capacities when compared with DC derived from freshly-isolated G-CSF mobilized PBSC. These DC also exhibited similar capacities in the primary allogeneic T-cell response.

Discussion: These results indicate that cryopreserved G-CSF mobilized PBSC cultured with GM-CSF/SCF/TNF-alpha gave rise to DC that were morphologically, phenotypically and functionally similar to DC derived from fresh G-CSF mobilized PBSC. The observation indicates the clinical usefulness of cryopreserved CD34+ cells from lymphoma patients.

MeSH terms

  • Antigens, CD34 / metabolism*
  • Cell Differentiation* / drug effects
  • Cryopreservation* / methods
  • Cytokines / pharmacology
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation
  • Flow Cytometry
  • Hematopoietic Stem Cell Mobilization
  • Humans
  • Lymphoma / blood*
  • Lymphoma / immunology*
  • Lymphoma / surgery
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD34
  • Cytokines