Abbreviations:iPSCs (Induced pluripotent stem cells), hiPS (Human iPS), CT scan (Computed tomography scan), TEM (Transmission electron microscopy), TV (Tidal volume), PEEP (Positive end-expiratory pressure), PIP (Peak inspirational pressure), AT-1 (Pneumocytes type 1), AT-2 (Pneumocytes type 2), h-HLA1 (Human leukocyte antigen 1), NKX2.1-GFP (Ubiquitously expressed green fluorescent protein under the pneumocytes progenitor marker (NKX2.1 gene) promoter), SPC-TdTomato (Ubiquitously expressed TdTomato protein under the surfactant (SPC gene) promoter), Hu (Hounsfield units), MLI (Mean linear intercept), Cdyn (Dynamic compliance), RV (Residual Volume), RVOT (Ventricular outflow tract), BAL (Bronchioalveolar lavage), PCO2 (Carbon dioxide partial pressure), PO2 (Oxygen partial pressure), mmHg (Milimeter mercury (Pressure)), ml/cmH2O (Centimeter water (Dynamic compliance)), a-Cap (Aerocytes), g-Cap (General capillary cells), h-CD31 (Human specific CD31), CD144 (Vascular endothelium cadherin), UEA-1-positive (Ulex europaeus agglutinin-I labelled cells), EdU (5-ethynyl-2'-deoxyuridine), VEGF-165 (Vascular endothelial growth factor 165), SFM (Serum free medium), EGM2 (Endothelial growth medium-2), FGF-7 (Fibroblast growth factor 7), FGF-10 (Fibroblast growth factor 10), RNU (Athymic nude rats), 4%PFA (4% Paraformaldehyde), DMEM (Dulbecco's Modified Eagle Medium), DPBS (Dulbecco's phosphate-buffered saline), CO2 (Carbon dioxide), HEPES (N-2-hydroxyethylpiperazine-N-2-ethane sulfonic acid), DAPI (4′,6-diamidino-2-phenylindole), DAB (3, 3'-diaminobenzidine), Ctrl (Control), SE (Standard error), ANOVA (Analysis of variance)
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Disclosure Statement: Dr. Harald Ott is the founder and CEO of IVIVA Medical
Funding Statement: This work was supported by a research grant by United Therapeutics Inc
Presentation: Presented at the AATS 102nd Annual Meeting, May 14-17, 2022, Boston, Massachusetts.
Central Picture Legend: Cell therapy ameliorates emphysema and improves vascularization.
iPSCs derived endothelial cells and pneumocytes incorporate into host gas exchange tissue and improve emphysema progression and vascularization.
The destruction of alveolar units and the resulting loss of diffusion capacity are the main features of emphysema. As a first step toward applying cellular therapy as a regenerative therapy we showed that iPSCs derived pneumocytes and endothelial cells can be delivered to the distal lung, engraft, and improve tissue structure and gas exchange function.