LR8 gene was first reported in a subpopulation of cultured human lung fibroblasts expressing the receptor for C1q-globular domain, and it was not detectable in cultured endothelial cells and smooth muscle cells. LR8 mRNA levels were higher in fibrotic lungs. In this study we assessed LR8 production in human tissues and determined if the distribution of fibroblasts producing LR8 is affected in fibrosis. Normal and fibrotic tissue sections from human liver, lung and kidneys were immunostained with antibodies to LR8 and examined for the presence of fibroblasts staining positively and negatively. The cells were also examined for co-expression of α-smooth muscle actin (SMA), a marker for myofibroblasts. The results showed that LR8 was expressed by fibroblasts, smooth muscle cells, endothelial cells, bile duct cells, pulmonary alveolar cells and distal and proximal kidney tubule cells. Connective tissues of normal and fibrotic tissues contained fibroblasts staining positively and negatively with anti- LR8 antibody. The number of LR8-positive cells was higher in fibrotic tissues, but differences were not statistically significant. Fibroblasts producing both LR8 and SMA were present in higher numbers in fibrotic tissues as compared to normal tissues and the differences were statistically significant (p<0.05). Our results show that fibroblast subtypes differing in LR8 expression are present in human tissues, and that in fibrotic tissues cells co-expressing LR8 and SMA are present. Our results indicate that LR8 expressing cells may participate in the early stages of fibrotic diseases and that fibroblasts expressing LR8, not LR8 negative cells, have potential to become myofibroblasts in fibrotic tissues.
In this review we discuss the historical perspective of stem cell populations from oral tissues in light of our current understanding of stem cell biology. Stem cells and their niches have been identified in the periodontium starting from the late 1970s. Applying new criteria for the identification and characterization reveals that oral tissues comprise a multipotent primitive neural crest-like stem cell population capable of differentiating into neural crest derived cell lineages of the cranial-facial zone. This population supplies cells to a more restricted stem cell type with tissue specific epigenetic memory that differentiates into cell lineages characteristic of their tissue origin. We believe that the microenvironment plays an essential role in maintaining stem cell populations and directing their migration and differentiation, and that this factor needs to be considered for utilization of stem cell-based therapy for periodontal regeneration and regenerative dental medicine.
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