Graduate Seminar Series: Cell and Tissue Stream
Graduate Seminar Series for the Institute of Biomedical Engineering (BME). This day is for cell and tissue stream presenters.
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Presentation Title: Rejuvenation of Type II Alveolar Epithelial Cells Using Interrupted Reprogramming to Reverse the Hallmarks of Aging
Abstract: Autologous lung cell therapy applications for the elderly are limited by suitable cell sources given cellular health declines with age. Alveolar type 2 (AT2) cells, noted to be the distal lung epithelial cell progenitor cell, have shown to be useful as a therapeutic cell source for a number of lung pathologies including Pulmonary Fibrosis. We look to identify aging hallmarks and use a novel transient reprogramming strategy to reverse damage resulting from age and disease. Our reprogramming approach is based on doxycycline-mediated induction of pluripotency stem cell genes, Oct4, Klf4, c-Myc, and Sox2 (OKMS), resulting in transient expression for a defined period, thus generating rejuvenated aged AT2-induced progenitor-like (AT2-iPL) cells. Our findings show that aged (≥65 years old) human AT2 cells have limited clonal potential and are functionally deficient compared to young (≤35 years old) AT2 cells. The aged alveolospheres are smaller and appear to have a different morphology which will be explored further. Aged AT2 cells have increased DNA damage and increased gene expression for senescence biomarkers including p21 and SA-β galactosidase- this might contribute to the lack of proliferation in aged alveolospheres. We look to add additional assays investigating telomere length and telomere maintenance genes, epigenetic marks, and mitochondrial health. After we have applied our interrupted reprogramming process to aged AT2 cells, we will characterize AT2-iPL cells and assess if they have restored functionality like young AT2 cells. Thus, providing a rejuvenated population for therapeutic use with the elimination of cell-intrinsic deficits after the reprogramming process.
Supervisor Name: Dr. Waddell
Year of Study: 4
Program of Study: PhD
Zoom link: https://us02web.zoom.us/j/89610372821?pwd=azd4SCtYVWtreVovaGNPV1c2NGY2Zz09
Meeting ID: 896 1037 2821
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