Engraftment of Bone Marrow-Derived Epithelial Cells

Abstract

The long-held concept that transplanted bone marrow (BM)-derived cells contribute only to cells of the hematopoietic system was challenged by data from our laboratory showing that a single male BM-derived cell could not only reconstitute the hematopoietic system of an irradiated female recipient, but could also lead to the generation of mature BM-derived epithelial cells in the liver, lung, skin, and gastrointestinal tract. Careful costaining and single-cell analyses have been used to rule out false positive cells due to inadequate detection techniques in microscopy or cell overlay. Since this initial discovery, we have sought to understand the mechanisms underlying the formation of BM-derived epithelial cells, and to evaluate their therapeutic use for gene therapy and/or tissue regeneration. Several reports have shown that donor BM-derived cells, possibly macrophages, can fuse with existing host epithelial cells to form heterokaryons that express both donor and tissue-specific markers. While this is certainly true for murine tyrosinemia models, we have used a Cre-lox system to demonstrate that fusion is not a requirement for the generation of BM-derived epithelial cells and is likely not responsible for the BM-derived epithelial cells generated after standard BM transplantation. In a proof of principal experiment for potential gene therapy applications, we have shown that autologous BM-derived cells transfected with a transgene prior to BM transplantation are able to develop into mature type-II pneumocytes that express the transgene. We also discuss future research directions in the field and the therapeutic potential of BM-derived epithelia, including ongoing work to test whether combined cell and gene therapy can be used therapeutically in preclinical mouse models of human disease.

Noninvasive Molecular Screening for Oral Precancer in Fanconi Anemia Patients

“…Reported mechanisms that could explain the presence of donor DNA in nonhematopoietic tissues are stem cell plasticity, fusion of bone marrow-derived blood cells with recipient cells, horizontal DNA transfer from donor to recipient cells, and contamination with donor leukocytes (36)(37)(38)(39)(40)(41)(42). Although we cannot exclude other mechanisms, our data strongly indicate a very simple source: leukocyte contamination.…”

Regeneration associated growth factor receptor and epithelial marker expression in lymphoid aggregates of ulcerative colitis

“…In inflammation, MET can be altered, because mesenchymal stem cells are mobilized to the sites of injury and consequently subjected to the inflammatory response (19). Although there are no data about a potential MET between these circumstances, it was published that bone marrow derived stem cells could differentiate into mature-appearing epithelial cells in response to tissue damage (20). Note: although the scale of magnification by virtual microscope may be varied from 0 to 1000Â, or even more, this scale is not continuous, and may be influenced by several technical factors (for more information visit www.3dhistech.com).…”

The Possible Role of Isolated Lymphoid Follicles in Colonic Mucosal Repair

“…Although there are no data about a potential MET beyong these circumstances, it was published that bone marrow derived stem cells could differentiate into mature-appearing epithelial cells in response to tissue damage [69].…”