Bone marrow stem cells do not repopulate the healthy upper respiratory tract

Abstract

Recent studies reported differentiation of both bone marrow and tissue-specific stem cells into cells of other organs. The demonstration that bone marrow stem cells differentiate into human hepatocytes in vivo has raised the possibility of new therapeutic approaches for liver disease. For diseases such as cystic fibrosis (CF), correction of the respiratory epithelium is being attempted by gene therapy. Differentiation of bone marrow stem cells into epithelium of the lung and airway was recently reported in an animal model, and would provide an alternative approach. We examined the nasal epithelium of female patients up to 15 years after gender-mismatched bone marrow transplantation. Donor-derived epithelial cells were sought with a combination of Y-chromosome fluorescence in situ hybridization and anti-cytokeratin antibody. In nasal brushing samples from 6 transplant-recipients, a median of 2.5% (range, 0.7-18.1%) of nuclei was male and identified as being of donor-origin. However, a complete absence of staining with anti-cytokeratin antibodies confirmed that these were not epithelial cells, but were likely to be either intraepithelial lymphocytes or mesenchymal cells. Following whole bone marrow transplantation, bone marrow progenitor cells do not differentiate into respiratory epithelium of the healthy upper airway. The differences between this and other studies could relate to the cells transplanted, to differential rates of turnover, or to the requirement for specific triggers to stimulate migration and differentiation. In the absence of such conditions, whole bone marrow transplantation is unlikely to provide a route for correction of the CF airway.

Pulmonary Epithelium: Cell Types and Functions

“…Other studies, however, have suggested that in some cases, bone marrow-derived cells may actually contribute to fibrosis (Epperly et al, 2003;Hashimoto et al, 2004;Phillips et al, 2004). Indeed, controversy remains about the actual ameliorative effect of circulating stem cells, whether or not they can engraft in other organs, and whether engrafted cells undergo fusion or transdifferentiation (Aliotta et al, 2005;Vassilopoulos et al, 2003;Wang et al, 2003;Chang et al, 2005;Davies et al, 2002;Kotton et al, 2005;Zander et al, 2005;Loi et al, 2006). Clearly, researchers have not yet reached a consensus about the role that circulating stem cells play in lung processes.…”

Efficient characterisation of human cell–bioceramic interactions in vitro and in vivo by using enhanced GFP-labelled mesenchymal stem cells

“…It is thus difficult to distinguish the implanted donor cells from the invading host cells. Human-specific antigens such as HLA or Y chromosome sequences [9] and human Alu sequences [4] have been used as human cell markers for hMSCs but detection requires refined techniques of immunocytochemistry or in situ hybridisation, for example. This makes it problematic to characterise the effects of the engineered products.…”

Long-Term Repopulation Effects of Donor BMDCs on Intestinal Epithelium

“…Wagers et al showed that transdifferentiation of circulating HSCs and/or their progeny is an extremely rare event, if it happens at all [25]. And it was reported that BMDCs would not repopulate the healthy upper respiratory tract [26]. Therefore, we doubted whether BMDCs could differentiate into intestinal epithelial cells in the long term in transplantation recipients and whether such a phenomenon would happen in recipients even without any special damage treatment.…”