15 February 2018

Stem cells in lung treatment

Chinese researchers from Tongji University, working under the guidance of Professor Wei Zuo, have made a breakthrough in the technology of regeneration of the human lung. In a pilot clinical trial, they managed to repair the damaged lungs of patients by transplanting their own lung stem cells.

Already in 2015, Professor Zuo and his colleagues identified adult p63+/Krt5+ stem cells in mouse lungs that have the potential to regenerate lung structures, including bronchioles and alveoli. However, as Professor Zuo notes, the anatomical structure and the process of development of the lungs of humans and mice differ significantly from each other. Therefore, only the study of human material can bring us closer to the truth and help us solve real medical problems.

As part of their subsequent work, the authors found that a population of basal cells carrying the SOX9+ marker is potentially capable of acting as human lung stem cells. These cells make up approximately 0.2% of the cells contained in the scrapings obtained during bronchoscopy. The authors learned how to isolate and multiply these cells in the laboratory while preserving their genetic stability and molecular phenotype.

To test the ability of lung stem cells to regenerate lung tissue in vivo, human stem cells were labeled with a green fluorescent protein and transplanted into the damaged lungs of immunodeficient mice. An autopsy performed 3 weeks after transplantation showed that the cells integrated into the mouse lung tissue over a sufficiently large area, forming a "chimeric organ".

Further histological analysis carried out using gold nanoparticle tagging technology demonstrated that stem cell transplantation provided successful regeneration of human bronchial and alveolar structures. In addition, areas of fibrosis in the damaged lungs of animals after stem cell transplantation were replaced with new human alveoli. At the same time, the results of the analysis of the gas composition of arterial blood indicated a significant recovery of pulmonary function.

Together with colleagues from the Southwestern Hospital at the University of the Chinese Army and the company Regend Therapeutics, the researchers began the first clinical study in which autologous lung stem cell transplantation was used to treat bronchiectasis. (Bronchial dilatation, or bronchiectasis, is irreversible damage to the bronchial structure of the lungs.) In March 2016, the study included the first 2 patients whose own lung stem cells were injected into their lungs using bronchoscopy.

A year after the transplant, both patients described relief of multiple respiratory symptoms, including cough and shortness of breath. Computed tomography has demonstrated regional restoration of expanded structures. Normalization of lung function in patients began 3 months after transplantation and continued throughout the one-year follow-up period.

Currently, the authors are conducting a multicenter clinical trial under placebo control, in which they have already performed 80 stem cell transplants to patients with various respiratory diseases, including bronchiectasis, chronic obstructive pulmonary disease and interstitial lung diseases.

For patients with chronic lung diseases, stem cell transplantation may be the most serious, if not the last hope. Professor Zuo believes that the new approach will make it possible to cope with such diseases in five years. He also notes that the safety and effectiveness of treatment mainly depends on the quality of the injected cells.

Article by Ma Qiwang et al. Regeneration of functional alveoli by adult human SOX9+ airway basal cell transplantation is published in the journal Protein & Cell.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert!: Chinese researchers report first lung stem cell transplantation clinical trial.


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