Differentiation of marrow-derived cells into epithelial cells

The focus on plasticity is based on a very exciting discovery in the Krause laboratory that bone marrow derived cells are capable of differentiating into non-hematopoietic cells throughout the body. In 2001, we published our finding that a single bone marrow derived cell could engraft the hematopoietic system and differentiate into mature epithelial cells in mice, and in 2002, we published that the same occurs in humans.

Since that time, we have focused on several important questions regarding this plasticity including which cell populations in the bone marrow are responsible for this plasticity, and how these cells are regulated. We have shown that bone marrow transplantation leads to amelioration of renal mesangial sclerosis, and we have shown that bone marrow derived cells can engraft as functional epithelial cells in the GI tract and airways of mice with cystic fibrosis. In studies to determine the mechanism(s) by which BM cells become epithelial cells, we have discovered that this involves at least 2 different mechanisms, one involving cell fusion and the other not. We hypothesize that hematopoietic cells can only take on the gene expression pattern of epithelial cells via cell fusion, but that other nonhematopoietic cells in the BM (and perhaps elsewhere), can differentiate into epithelial cells without cell fusion.