Regeneration of functional alveoli by adult human SOX9 airway basal cell transplantation

Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9 basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9 BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9 BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient's lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9 BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.

Effect of the different intravenous anesthetics on the levels of four neuropeptides in patients with hypertension during induction / 中华麻醉学杂志

95mmHg) were randomly divided into 3 equal groups of 20 each : thiopental group, etomidate group and propofol group. All patients were prmedicated with intramuscular phenobarbital 0. 1g and atropine 0.5mg. Anesthesia was induced with thiopental 4mg?kg-1 or etomidate 0.3mg?kg-1 or propofol 2mg?kg-1, midazolam 0.1mg?kg-1, fentanyl 5?g?kg-1 and vecuronium 0.1mg?kg-1 and maintained with isoflurane inhalation and intermittent boluses of fentanyl and vecuronium. Blood samples were taken before anesthesia(To), 2min after induction(T1) and 2 and 10 min after tracheal intubation (T2, T3) for determination of plasma levels of endothelin(ET), calcitonin gene-related peptide(CGRP), neuropeptide Y (NPY) and neurotensin (NT). Results The three groups were compared with regard to age, sex and weight. BP significantly decreased after induction with thiopental or propofol but increased significantly after intubation in thiopental group and etomidate group. ET and NPY decreased but CGRP and NT increased significantly after induction in thiopental and propofol group. The plasma levels of all four neuropeptides increased significantly after tracheal intubation in thiopental and etomidata group but remained unchanged in propofol group. Conclusions Propofol is the intravenous anesthetic of choice for induction of anesthesia in patients with hypertension.