Lung Cell Transplantation for Pulmonary Fibrosis

Authors

Irit Milman Krentsis
Yangxi Zheng
Chava Rosen
Sarah Y Shin
Christa Blagdon
Einav Shoshan
Yuan Qi
Jing Wang
Sandeep K Yadav
Esther Bachar Lustig
Elias Shetzen
Burton F Dickey
Harry Karmouty-Quintana
Yair Reisner

Publication Date

8-23-2024

Journal

Science Advances

Abstract

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors expanded to form numerous donor-derived patches comprising AT1 and AT2 alveolar cells, as well as donor-derived mesenchymal and endothelial cells. This lung chimerism was associated with attenuation of fibrosis, as demonstrated histologically, biochemically, by computed tomography imaging, and by lung function measurements. Our study provides a strong rationale for the treatment of lung fibrosis using lung cell transplantation.

Keywords

Animals, Mice, Disease Models, Animal, Bleomycin, Pulmonary Fibrosis, Lung, Idiopathic Pulmonary Fibrosis, Lung Transplantation

Comments

Supplementary Materials

PMID: 39178253