Chemoattraction of CD34+ progenitor cells and dendritic cells to the site of tumor excision as the first step of an immunotherapeutic approach to target residual tumor cells.
The authors previously showed that C34+ progenitor cells are mobilized into the peripheral blood in tumor bearers. The current study used a murine Lewis lung carcinoma (LLC) model to examine if the CD34+ cells can be chemoattracted to a tumor excision site as the first step to inducing differentiation of the attracted CD34+ cells into immune stimulatory dendritic cells (DC). Upon tumor excision, gelatin sponges were implanted into the surgical site and infused with phosphate-buffered saline or vascular endothelial cell growth factor (VEGF). The implants were removed after 4, 7, 14, and 21 days and analyzed for their cellular content. The incorporation of VEGF into implants increased the accumulation of CD34+ cells early after implantation. By day 21, the CD34+ cell content declined. However, the numbers of DCs became increased in the VEGF-containing sponges and this persisted throughout the 3-week duration of the study. The VEGF-containing implants contained a lower percentage of CD11b+ myeloid cells for the first 2 weeks after implantation as compared with the control implants. By 21 days, myeloid cell numbers declined in the control and VEGF implants. Since endothelial cell precursors have a common precursor with myeloid progenitor cells, the implants were also examined for their endothelial cell content. With increasing time after implantation, the number of endothelial cells and formation of vessel-like structures became greater in the VEGF-containing implant as compared with the control implants. These results show the feasibility of using VEGF-containing sponges to attract DC precursors and to increase the number of DCs at the tumor excision site.
Banich
James C
JC
Department of Otolaryngology, Loyola University Stritch School of Medicine, Maywood, U.S.A.
Kolesiak
Kristin
K
Young
M Rita I
MR
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology*; D001707:Biopsy, Needle; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002633:Chemotaxis / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology*; D016228:Endothelial Growth Factors / Q000276:immunology / Q000494:pharmacology*; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000494:pharmacology*; D008222:Lymphokines / Q000276:immunology / Q000494:pharmacology*; D012016:Reference Values; D012680:Sensitivity and Specificity; D013234:Stem Cells / Q000502:physiology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors