Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation

Bruscia, Emanuela M.; Price, Joanna E.; Cheng, Elaine; Weiner, Scott A; Caputo, Christina; Ferreira, Elisa Carvalho; Egan, Marie E.; Krause, Diane S.

doi:10.1073/pnas.0510758103

Cited by 70 publications

(62 citation statements)

References 33 publications

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“…This includes only rare engraftment and CFTR expression in airway epithelium following transplantation of adult marrow-derived cells containing wildtype CFTR to CFTR KO mice [21] (Figure 2). Comparable low level engraftment was observed in intestinal epithelium of CFTR KO mice following transplant with wildtype marrow-derived cells [23]. As such, many of the earlier findings suggesting more substantial engraftment are now felt to be technical artifacts.…”

Section: Lung Repair and Remodeling With Adult Bone Marrow-derived Stmentioning

confidence: 99%

Stem cells and cell therapies for cystic fibrosis and other lung diseases

Weiss

2008

Pulmonary Pharmacology & Therapeutics

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This review will critically evaluate recent findings suggesting that embryonic stem cells and stem cells derived from adult tissues, including bone marrow and umbilical cord blood, may be utilized in repair and regeneration of injured or diseased lungs. This is an exciting and rapidly moving field that holds promise as a novel therapeutic approach for cystic fibrosis and other lung diseases. However, while early studies suggested substantial lung remodeling, particularly with bone marrow-derived cells, more recent findings suggest that engraftment of adult marrow-derived cells in lung is a rare event of uncertain significance. Most recently, it has been suggested that a more relevant role of adult marrow-derived stem cells in lung is modulation of local inflammatory and immune responses. This review will also describe recent advances in understanding of local stem and progenitor cells in lung and their roles in lung development and repair.

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Section: Lung Repair and Remodeling With Adult Bone Marrow-derived Stmentioning

confidence: 99%

Stem cells and cell therapies for cystic fibrosis and other lung diseases

Weiss

2008

Pulmonary Pharmacology & Therapeutics

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“…Bone marrow (BM) transplantation was performed as previously described (7,27). Briefly, BM cells were isolated from the femurs of WT or CF mice.…”

Section: Mousementioning

confidence: 99%

“…BALF was collected using standard methods. The dilution of epithelial lining fluid recovered with BAL was calculated on the basis of the blood urea nitrogen concentration in the plasma, as previously described (7,20). BALF was stored in single-use aliquots at Ϫ80°C until analysis.…”

Section: Mousementioning

confidence: 99%

Increased susceptibility of Cftr^−/− mice to LPS-induced lung remodeling

Bruscia

Zhang

Barone

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Cystic fibrosis (CF) is caused by homozygous mutations of the CF transmembrane conductance regulator (CFTR) Cl− channel, which result in chronic pulmonary infection and inflammation, the major cause of morbidity and mortality. Although these processes are clearly related to each other, each is likely to contribute to the pathology differently. Understanding the contribution of each of these processes to the overall pathology has been difficult, because they are usually so intimately connected. Various CF mouse models have demonstrated abnormal immune responses compared with wild-type (WT) littermates when challenged with live bacteria or bacterial products acutely. However, these studies have not investigated the consequences of persistent inflammation on lung tissue in CF mice, which may better model the lung pathology in patients. We characterized the lung pathology and immune response of Cftr−/− (CF) and Cftr+/+ (WT) mice to chronic administration of Pseudomonas aeruginosa lipopolysaccharide (LPS). We show that, after long-term repeated LPS exposure, CF mice develop an abnormal and persistent immune response, which is associated with more robust structural changes in the lung than those observed in WT mice. Although CF mice and their WT littermates develop lung pathology after chronic exposure to LPS, the inflammation and damage resolve in WT mice. However, CF mice do not recover efficiently, and, as a consequence of their chronic inflammation, CF mice are more susceptible to morphological changes and lung remodeling. This study shows that chronic inflammation alone contributes significantly to aspects of CF lung pathology.

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“…These findings suggest a possible therapeutic role for stem cells in the treatment of cystic fibrosis (CF) and other chronic lung diseases. For example, if stem cells expressing normal cystic fibrosis transmembrane conductance regulator (CFTR) can be induced to repopulate the airway epithelium, then much of the morbidity associated with CF could potentially be reduced (4)(5)(6). However, investigations using human embryonic stem cells are currently limited by scientific, ethical, and political considerations (7,8).…”

mentioning

confidence: 99%