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NPJ Regen Med. 2019 Aug 20;4:17. doi: 10.1038/s41536-019-0080-9. eCollection 2019.

Mesenchyme-free expansion and transplantation of adult alveolar progenitor cells: steps toward cell-based regenerative therapies.

Author information

1
1Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
2
2Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
3
3Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104 USA.
4
4Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
5
5Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
6
6Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
7
7Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104 USA.
8
8Division of Neonatology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.

Abstract

Alveolar type-2 (AT2) cells are necessary for the lung's regenerative response to epithelial insults such as influenza. However, current methods to expand these cells rely on mesenchymal co-culture, complicating the possibility of transplantation following acute injury. Here we developed several mesenchyme-free culture conditions that promote growth of murine AT2 organoids. Transplanting dissociated AT2 organoids into influenza-infected mice demonstrated that organoids engraft and either proliferate as AT2 cells or unexpectedly adopt a basal cell-like fate associated with maladaptive regeneration. Alternatively, transplanted primary AT2 cells also robustly engraft, maintaining their AT2 lineage while replenishing the alveolar type-1 (AT1) cell population in the epithelium. Importantly, pulse oximetry revealed significant increase in blood-oxygen saturation in primary AT2 recipients, indicating that transplanted cells also confer increased pulmonary function after influenza. We further demonstrated that both acid installation and bleomycin injury models are also amenable to AT2 transplantation. These studies provide additional methods to study AT2 progenitor potential, while serving as proof-of-principle for adoptive transfer of alveolar progenitors in potential therapeutic applications.

KEYWORDS:

Adult stem cells; Regeneration

Conflict of interest statement

Competing interestsThe authors declare no competing interests.

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