Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date. Angiotensin-converting enzyme 2 (ACE2) plays a fundamental role in SARS-CoV-2 pathogenesis because it allows viral entry into host cells. Here we show that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection. Our results suggest that LSC-nanodecoys can serve as a potential therapeutic agent for treating COVID-19. 

This study helps set the stage for the transition of this cellular therapy paradigm from rodent models to clinical trials in a number of ways. The transbronchial acquisition of the lung spheroid cells is a minimally invasive strategy suitable for the clinic and preferable to thoracoscopic alternatives; the doses used in this study are scalable, manufacturable, and comparable to currently existing clinical trial efforts targeting other lung diseases; and the intravenous route of administration used is applicable to clinical trials, as it presents an easy, quick, and patient‐friendly way to administer the treatment. 

We have demonstrated the safety and efficacy of lung spheroid cell- secretome and exosomes (LSC-Sec and LSC-Exo, respectively) inhalation therapy in pulmonary fibrosis animal models. LSC-Sec and -Exo inhalation therapy attenuating the progression and severity of pulmonary fibrosis, decreasing apoptosis and collagen deposition, protecting alveolar structures, increasing angiogenesis, and resorted pulmonary function in a series of three mice and rat models of pulmonary fibrosis. Non-invasive and repeated inhalation therapy can potentially provide a viable off-the-shelf therapeutic for IPF patients. Our study showed the potential of LSC-Sec and -Exo as an acellular therapy alternative option for patients suffering from IPF.  

The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis.​ 

We have demonstrated the safety and efficacy of allogeneic lung spheroid cell (LSC) treatment in attenuating the progression and severity of pulmonary fibrosis, decreasing apoptosis, protecting alveolar structures, and increasing angiogenesis in rats. The use of allogeneic stem cells can potentially change the way we perform cell therapies by allowing for the growth of large quantities of cells from numerous sources, including donated lungs not used for transplantations, surgical discards, and lungs from recently deceased cadavers. Our study demonstrates the potential of allogeneic LSCs as a viable future therapy option for patients suffering from idiopathic pulmonary fibrosis.  

For the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).​