Cell Therapy for Cystic Fibrosis Lung Disease: Regenerative Basal Cell Amplification
| Autor: | Alfahdah Alsudayri, Scott W. Lallier, Mahelet Tadesse, Cynthia L Hill, Susan D. Reynolds, Don Hayes, Cynthia M. Schwartz, Benjamin T. Kopp |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Cell division Adolescent Cystic Fibrosis Cell Cell- and Tissue-Based Therapy Cystic Fibrosis Transmembrane Conductance Regulator Respiratory Mucosa Biology Stem Epithelium Cell therapy 03 medical and health sciences Basal (phylogenetics) Young Adult 0302 clinical medicine medicine Humans Regeneration Child Lung Cell Proliferation Infant Cell Differentiation Epithelial Cells Cell Biology General Medicine Middle Aged Molecular biology Transplantation Airway 030104 developmental biology medicine.anatomical_structure Child Preschool Basal cell Respiratory epithelium Female Stem cell 030217 neurology & neurosurgery Developmental Biology Tissue‐Specific Progenitor and Stem Cells Progenitor |
| Zdroj: | Stem Cells Translational Medicine |
| ISSN: | 2157-6564 |
| Popis: | The human airway epithelium is regenerated by basal cells. Thus, basal cell therapy has the potential to cure cystic fibrosis (CF) lung disease. We previously reported that the human basal cells repopulated the mouse airway epithelium after transplantation, and we estimated that 60 million cells would be needed to treat a human patient. To further develop cell therapy, we compared the proliferation potential of non-CF and CF tissue-derived bronchial basal cells. Three methods were used: regenerative cell frequency, burst size, and cell division frequency. Second, we used a serial passage strategy to determine if CF basal cells could be amplified to the estimated therapeutic dose. These studies evaluated that tissue-derived bronchial basal cells and the basal cells that were recovered by brushing bronchial airways or the nasal respiratory epithelium. Finally, we used the limiting dilution method to isolate non-CF and CF basal cell clones. The proliferation assays and the air-liquid-interface differentiation method were used to determine if cell amplification altered the proliferation and/or differentiation potential of clonal isolates. We demonstrate that: (a) non-CF and CF basal cell proliferation is similar, (b) CF basal cells can be amplified to a therapeutic cell dose, and (c) amplified non-CF and CF basal cell clones differentiate normally. Despite these encouraging findings, we also find that the cell amplification process depletes the regenerative basal cell pool. Analysis of basal cell clones indicates that serial passage selects for long-lived basal cells and raise the possibility that prospective isolation of these stem-like cells will improve the efficacy of cell replacement therapy. Stem Cells Translational Medicine 2019;8:225&235 |
| Databáze: | OpenAIRE |
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