Stem Cell-Induced Pulp Regeneration Can Be Enhanced by Administration of CCL11-Neutralizing Antibody in the Ectopic Tooth Transplantation Model in the Aged Mice.

Abstract

Pulp regeneration by stem cell transplantation declines due to age-related reduction. We hypothesized that administration of a cytokine together with the cell transplantation may improve the stem cell niche microenvironment and promote regeneration. CCL11 is implicated as a factor in aging. This investigation was performed to investigate the changes in the quality of the regenerated pulp by administration of CCL11 antibody in the aged mice and elucidate the underlying mechanisms. Mobilized dental pulp stem cell (MDPSC) transplants were characterized in an ectopic tooth root transplantation model in both the aged and young mice. The amount of regenerated pulp tissue was analyzed in the transplants with continuous administration of CCL11 antibody compared with those without the antibody administration. Blood CCL11 levels were assessed at the onset of the experiment. Furthermore, immunostaining of CD68 together with CD11c or CD206 for M1 and M2 macrophage, respectively, were performed. Each double-positive cell count of M1 and M2 macrophages and M1/M2 ratio in the transplants with administration were compared with those without administration both in the aged and young mice. The administration of CCL11 antibody enhanced pulp regeneration and significantly reduced the blood CCL11 level in the aged mice. As the number of M1 macrophages decreased, the M1/M2 ratio in the treated aged mouse was less than that in the untreated aged mouse. There was, however, significant difference between the treated aged mouse and the untreated young mouse. CCL11 antibody has the potential to enhance and stimulate pulp regeneration in the aged mice.