Repair of injured lungs represents a longstanding therapeutic challenge. We show that human and mouse embryonic lung tissue from the canalicular stage of development (20-22 weeks of gestation for humans, and embryonic day 15-16 (E15-E16) for mouse) are enriched with progenitors residing in distinct niches. On the basis of the marked analogy to progenitor niches in bone marrow (BM), we attempted strategies similar to BM transplantation, employing sublethal radiation to vacate lung progenitor niches and to reduce stem cell competition. Intravenous infusion of a single cell suspension of canalicular lung tissue from GFP-marked mice or human fetal donors into naphthalene-injured and irradiated syngeneic or SCID mice, respectively, induced marked long-term lung chimerism. Donor type structures or 'patches' contained epithelial, mesenchymal and endothelial cells. Transplantation of differentially labeled E16 mouse lung cells indicated that these patches were probably of clonal origin from the donor. Recipients of the single cell suspension transplant exhibited marked improvement in lung compliance and tissue damping reflecting the energy dissipation in the lung tissues. Our study provides proof of concept for lung reconstitution by canalicular-stage human lung cells after preconditioning of the pulmonary niche.

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The ideal technique for identifying the epidural space remains unclear. Five-hundred-forty-seven women in labor who requested epidural analgesia were randomly allocated to three groups according to the technique by which the epidural space was identified: 1) loss-of-resistance with air (air; n = 180), 2) loss-of-resistance with lidocaine (lidocaine; n = 185), and 3) loss-of-resistance with both air and lidocaine (air-plus-lidocaine; n = 182). We assessed ease of epidural catheter insertion, characteristics of the blockade, quality of analgesia, and complications. The inability to thread the epidural catheter occurred in 16% of the air, 4% of the lidocaine, and 3% of the air-plus-lidocaine patients (P < 0.001). More patients from the air group had unblocked segments (6.6% versus 3.2% and 2.2%, respectively; P < 0.02). The incidence of accidental dural puncture was greater in the air group (1.7% versus 0% in the other two groups; P < 0.02). Pain scores, time to onset of analgesia, upper sensory level, motor blockade, and the incidence of hypotension, transient neurological deficits, postpartum urinary retention, and postdural puncture headache were comparable. Identification of the epidural space with air was more difficult and caused more dural punctures than with lidocaine or air plus lidocaine. Additionally, sequential use of air and lidocaine had no advantage over lidocaine alone.