Bone marrow cells contribute to tissue regeneration in the intestine and skin

Adult bone marrow contains progenitor cells that can extricate themselves from their bone marrow cavity niche, and engraft within foreign tissues, whereupon they produce specific differentiated adult lineages. Bone marrow engraftment is upregulated with increasing regenerative pressure, which has triggered speculation as to the therapeutic potential of bone marrow cells. In this thesis, I describe for the first time, that transplanted adult bone marrow cells engraft within the intestines of mice and humans and give rise to a substantial proportion of the mesenchymal cells in the lamina propria, namely, the intestinal subepithelial myofibroblasts. I show that bone marrow contribution to intestinal myofibroblasts is significantly enhanced in a mouse model of colitis. Furthermore, I show that bone marrow cells form multiple vascular lineages in the mouse colon, with an enhanced propensity in colitis. These results have implications for the use of bone marrow in the treatment of inflammatory bowel disease, either by directly producing mesenchymal and vascular lineages, and/or possibly via the indirect regulation of intestinal epithelial cells. I also report that transplanted bone marrow cells engraft into the skin and contribute to multiple epidermal lineages. These bone marrow-derived cells are commonly located within postulated epidermal stem cell niches, and can express putative epidermal stem cell markers. Bone marrow cell engraftment was significantly enhanced in the wounded epidermis, and bone marrow-derived epidermal cells can proliferate in vivo, and form colonies in vitro. I found no evidence that bone marrow cells fuse with indigenous epidermal cells to form heterokaryons. These results highlight the potential of bone marrow cells in the treatment of diseases of the gastrointestinal tract and skin.