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Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis 总被引:22,自引:0,他引:22
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Wang G Bunnell BA Painter RG Quiniones BC Tom S Lanson NA Spees JL Bertucci D Peister A Weiss DJ Valentine VG Prockop DJ Kolls JK 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(1):186-191
Cystic fibrosis (CF), the most prevalent, fatal genetic disorder in the Caucasian population, is caused by mutations of CF transmembrane conductance regulator (CFTR). The mutations of this chloride channel alter the transport of chloride and associated liquid and thereby impair lung defenses. Patients typically succumb to chronic bacterial infections and respiratory failure. Restoration of the abnormal CFTR function to CF airway epithelium is considered the most direct way to treat the disease. In this report, we explore the potential of adult stem cells from bone marrow, referred to as mesenchymal or marrow stromal stem cells (MSCs), to provide a therapy for CF. We found that MSCs possess the capacity of differentiating into airway epithelia. MSCs from CF patients are amenable to CFTR gene correction, and expression of CFTR does not influence the pluripotency of MSCs. Moreover, the CFTR-corrected MSCs from CF patients are able to contribute to apical Cl(-) secretion in response to cAMP agonist stimulation, suggesting the possibility of developing cell-based therapy for CF. The ex vivo coculture system established in this report offers an invaluable approach for selection of stem-cell populations that may have greater potency in lung differentiation. 相似文献
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Rebecca N. Baergen Manuel M. Castillo Blesilda Mario-Singh Arthur J. Stehly Kurt Benirschke 《Fetal and pediatric pathology》1997,17(1):159-168
We describe a case of a 19-year-old G1P0 woman with an unremarkable prenatal course who presented at term in labor. Fetal bradycardia developed and forceps were used to deliver a male infant, who was born with Apgar scores of 0 and 0 and could not be resuscitated. Examination at autopsy revealed no gross evidence of trauma, but on microscopic examination of the lungs and the placenta, multiple fetal vessels contained emboli consisting of fragments of fetal cerebellar cortex. Previously reported cases of this rare phenomenon are reviewed and the pathogenesis is discussed. 相似文献
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Erik E. Folch Michael A. Pritchett Michael A. Nead Mark R. Bowling Septimiu D. Murgu William S. Krimsky Boris A. Murillo Gregory P. LeMense Douglas J. Minnich Sandeep Bansal Blesilda Q. Ellis Amit K. Mahajan Thomas R. Gildea Rabih I. Bechara Eric Sztejman Javier Flandes Otis B. Rickman Sadia Benzaquen Michael Zgoda 《Journal of thoracic oncology》2019,14(3):445-458
Introduction
Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology that guides endoscopic tools to pulmonary lesions. ENB has been evaluated primarily in small, single-center studies; thus, the diagnostic yield in a generalizable setting is unknown.Methods
NAVIGATE is a prospective, multicenter, cohort study that evaluated ENB using the superDimension navigation system (Medtronic, Minneapolis, Minnesota). In this United States cohort analysis, 1215 consecutive subjects were enrolled at 29 academic and community sites from April 2015 to August 2016.Results
The median lesion size was 20.0 mm. Fluoroscopy was used in 91% of cases (lesions visible in 60%) and radial endobronchial ultrasound in 57%. The median ENB planning time was 5 minutes; the ENB-specific procedure time was 25 minutes. Among 1157 subjects undergoing ENB-guided biopsy, 94% (1092 of 1157) had navigation completed and tissue obtained. Follow-up was completed in 99% of subjects at 1 month and 80% at 12 months. The 12-month diagnostic yield was 73%. Pathology results of the ENB-aided tissue samples showed malignancy in 44% (484 of 1092). Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 69%, 100%, 100%, and 56%, respectively. ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher pneumothoraces (requiring admission or chest tube placement) occurred in 2.9%. The ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher bronchopulmonary hemorrhage and grade 4 or higher respiratory failure rates were 1.5% and 0.7%, respectively.Conclusions
NAVIGATE shows that an ENB-aided diagnosis can be obtained in approximately three-quarters of evaluable patients across a generalizable cohort based on prospective 12-month follow-up in a pragmatic setting with a low procedural complication rate. 相似文献5.
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