Induction of alveolar and bronchiolar phenotypes in human lung organoids.

Patient-derived organoids have revolutionized biomedical research and therapies by "transferring the patient into the Petri dish". In vitro access to human lung organoids representing distal lung tissue, i.e. alveolar organoids, would facilitate research pertaining to a wide range of medical conditions and might open for a future approach to individualized treatment.We propose a protocol to derive a single human lung biopsy towards both alveolar and bronchiolar organoids. By modulating Wnt pathway, we obtained a differential gene expression of the main markers for both subtypes, such as a higher expression of surfactant protein C in alveolar organoids or a higher expression of mucine 5AC in bronchiolar organoids. Although the specific cell enrichment was not complete, the differentiation was observed as early as passage 1 based on morphology, and confirmed by QPCR and histology at passage 2. These results are consistent with a functional specification of lung epithelium towards both alveoli- and bronchi-enriched organoids from first passages.

Effective Hemostasis in Severe Mesenteric Vein Laceration with Tachosil(®), using a Low- or Non-thrombogenic Patch to Prevent Tachosil(®)-induced Thrombosis.

Fibrinogen- and thrombin-coated collagen fleece (FTCC) facilitates surgical hemostasis, and is of particular value during resection of parenchymatous organs. Since thrombosis may ensue if the preparation is unintentionally applied intravascularly, it has not been recommended for treating lacerations of large veins, and no previous reports describe its use in vein repair. Our observations in two patients suggest, however, that FTCC might be indicated for hemostasis in vein injury where vascular suture is difficult or not possible, provided a low- or non-thrombogenic patch is interposed to prevent FTCC-induced vein thrombosis. Our two patients had severe lacerations of the proximal superior mesenteric vein (SMV) not amenable to conventional vein repair. Rapid hemostasis was obtained without suturing using Tachosil(®), an FTCC preparation, covered with omentum. In the first patient hemostasis was obtained at the expense of vein thrombosis, apparently due to contact between the coagulant-containing side of Tachosil(®) and the inside of the vein wall. In our second patient we therefore put a small patch of parietal peritoneum on the section of the Tachosil(®) targeted to cover the vein tear to avoid direct contact between Tachosil(®) and the vein lumen. Ultrasound examination 3 days postoperatively, and autopsy 11.5 months later showed that the vein was widely patent with no stenosis or thrombus. Our observations in these two patients were that an FTCC-omentum pack alone secured rapid hemostasis in severe SMV laceration, and when a peritoneal patch was interposed between FTCC and a lacerated SMV, FTCC-induced vein thrombosis did not occur.