Bone marrow cells can become functional gut lining cells

Researchers report the discovery that cells used in bone marrow transplantation can develop into new cells lining the gut, according to a study by Yale School of Medicine in the Proceedings of the National Academy of Sciences.

The study showed that bone marrow derived cells can differentiate into functional gastrointestinal epithelial cells after bone marrow transplantation. Research was from the laboratory of Diane Krause, M.D., professor of Laboratory Medicine and senior author of the study, in collaboration with Marie Egan, M.D., associate professor of pediatrics, respiratory medicine, and cellular and molecular physiology.

"We demonstrated that the cells were functional by showing that they express functional chloride channels (known as CFTR, or cystic fibrosis transmembrane conductance regulator) which are necessary for fluid balance in the gut," Krause said.

The researchers used mice that do not have this chloride channel. After bone marrow transplantation from donor mice that do have the chloride channel, recipient mice had some normal chloride channel activity.

Alhough this is exciting, the levels of donor derived gut cells are currently far too low to be used as a treatment for cystic fibrosis, an inherited disease in which the organs, especially those of the pancreas, lungs, and intestines, become clogged with thick mucus.

"We hope this finding will have implications for cystic fibrosis, but this is a first step and there are many, many more years of research to be done before we can determine this," said Krause.

 

 

Bruscia EM, et al. Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation. Proc Natl Acad Sci U S A. 2006 Feb 15; [Epub ahead of print]

Departments of *Laboratory Medicine, Pediatrics, and Cellular and Molecular Physiology, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520.

Several studies have demonstrated that bone marrow (BM)-derived cells give rise to rare epithelial cells in the gastrointestinal (GI) and respiratory tracts after BM transplantation into myeloablated recipients. We investigate whether, after transplantation of cystic fibrosis transmembrane conductance regulator (CFTR)-positive BM-derived cells, BM-derived GI and airway epithelial cells can provide CFTR activity in the GI tract and nasal epithelium of recipient cystic fibrosis mice. CFTR-/- mice were transplanted with wild-type BM after receiving different doses of irradiation, and CFTR activity was assessed in vivo in individual mice over time by using rectal and nasal potential difference analyses and in vitro by Ussing chamber analysis. The data suggest that rare BM-derived epithelial cells in the GI and nasal epithelium detected in CFTR-/- transplanted mice provide a modest level of CFTR-dependent chloride secretion. Detection of CFTR mRNA and protein in tissues of transplanted CFTR-/- mice supports these data.