Document Type : Original Article
STEM CELLS DEPARTMENT, ROYAN INSTITUTE, TEHRAN, IRAN
Objective: The present study examines the effects of increased heat shock proteins expression in MDA-MB468 adeno-carcinoma cells on expansion and differentiation of hematopoetic stem cells from human umbilical cord blood.
Materials and Methods: Highly purified human CD34+ cells (Magnetic bead isolation) derived from umbilical cord blood were cultured, under three conditions, in the presence of FLt3L, SCF, GMCSF, IL-3, TPO and MDA-MB 468 Carcinoma lysate (MDA); heat treated MDA-MB468 lysate (MDA-HSP) or without tumor lysate as control group. Flow cytometry and direct scoring of solid cultures were done to evaluate the proliferation, and colony forming ability and surface markers of CD34+ Cells on days 0, 7 and 14 of culture.
Results: Long term culture of CD34+ Cells in the presence of tumor lysates caused their differentiation with decrease in cell expansion and colony forming unit potency. Phenotype of cultured cells was changed toward myeloid or lymphoid lineages. Comparison of the three groups showed that, MDA caused the lowest proliferation and CFC followed MDA-HSP. Among the groups, MDA and MDA-HSP, Stimulated the differentiation toward lymphoid cells Specially B Cells (CD19+), NK cells (CD56+) and myeloid progenitor cells (CD14+).However, CD14+ increased in control group.
Conclusion: Tumor cells contain substances regulating development and decreasing proliferation and colony forming potential of HSCs. Heat treated tumor cells contain HSPs and other substances preserving some expansion and colony forming properties of hematopoietic stem cells. It could be argued that these substances may cause differentiation of HSCs into immune cells such as NK and myeloid cells that induce strong anti tumor immune responses.