Using ex vivo bioengineered lungs to model pathologies and screening therapeutics: A proof-of-concept study.

Respiratory diseases, claim over eight million lives annually. However, the transition from preclinical to clinical phases in research studies is often hindered, partly due to inadequate representation of preclinical models in clinical trials. To address this, we conducted a proof-of-concept study using an ex vivo model to identify lung pathologies and to screen therapeutics in a humanized rodent model. We extracted and decellularized mouse heart-lung tissues using a detergent-based technique. The lungs were then seeded and cultured with human cell lines (BEAS-2B, A549, and Calu3) for 6-10 days, representing healthy lungs, cancerous states, and congenital pathologies, respectively. By manipulating cultural conditions and leveraging the unique characteristics of the cell lines, we successfully modeled various pathologies, including advanced-stage solid tumors and the primary phase of SARS-CoV-2 infection. Validation was conducted through histology, immunofluorescence staining, and pathology analysis. Additionally, our study involved pathological screening of the efficacy and impact of key anti-neoplastic therapeutics (Cisplatin and Wogonin) in cancer models. The results highlight the versatility and strength of the ex vivo model in representing crucial lung pathologies and screening therapeutics during the preclinical phase. This approach holds promise for bridging the gap between preclinical and clinical research, aiding in the development of effective treatments for respiratory diseases, including lung cancer.

International Travel for Organ Transplantation: A Survey of Professional Experiences and Attitudes Toward Data Collection and Reporting.

Background: Lack of data regarding international travel for organ transplantation (ITOT) hampers efforts to evaluate, understand, and respond to trends in ITOT activities, such as those suggestive of organ trafficking or "transplant tourism." This study aimed to assess transplant professionals' experience of ITOT and their attitudes toward reporting ITOT data to a global registry. Methods: An international cross-sectional anonymous survey of transplant professionals was conducted online (from October to December 2022). The English language questionnaire assessed professional experiences in providing care to individuals who had traveled to or from a country for living donation or transplantation, and attitudes toward reporting of ITOT data. Data were analyzed with descriptive statistics. Results: Two hundred thirty-nine individuals from 68 countries completed the entire questionnaire, of whom 79% had provided care for ≥1 patient who had traveled internationally for donation or transplantation. Of these, 60.8% of individuals (n = 115) had cared for ≥1 person who engaged in ITOT between 2019 and 2022, with the most recent case experiences involving 89 countries and 157 unique routes of international travel. Predominant concerns regarding reporting of ITOT data to a global registry related to prevention of harm and protection of patient privacy; most (52.7%; n = 126) respondents expressed a preference for anonymous reporting of ITOT data. Conclusions: ITOT is a global phenomenon and transplant professionals' experience with ITOT cases is more common than anticipated. Systems for the collection of ITOT activity data should be carefully designed to address potential ethical concerns of transplant professionals which may influence reporting practices.

Mesenchymal cells support the early retention of primary alveolar type 2 cells on acellular mouse lung scaffolds.

Objectives: Tissue engineering approaches via repopulation of acellular biological grafts provide an exciting opportunity to generate lung grafts for transplantation. Alveolar type 2 (AT2) cells are a promising cell source for re-epithelialization. There are however inherent limitations with respect to their survival and growth, thus impeding their usability for tissue engineering applications. This study investigates the use of mesenchymal stromal cells to support primary AT2 cells for recellularization of mouse lung scaffolds. Methods: AT2 cells and bone marrow-derived mesenchymal cells (BMC) were co-delivered to decellularized mouse lung scaffolds. Recellularized lungs were evaluated for cell surface coverage, viability, and differentiation at 1 and 4 days after cell seeding. Recellularization was evaluated via histological analysis and immunofluorescence. Results: Simultaneous delivery of AT2 and BMC into acellular lung scaffolds resulted in enhanced cell surface coverage and reduced AT2 cell apoptosis in the recellularized scaffolds at Day 1 but not Day 4. AT2 cell number decreased after 4 days in both of AT2 only and codelivery groups suggesting limited expansion potential in the scaffold. After retention in the scaffold, AT2 cells differentiated into Aqp5-expressing cells. Conclusions: Our results indicate that BMC support AT2 cell survival during the initial attachment and engraftment phase of recellularization. While our findings suggest only a short-term beneficial effect of BMC, our study demonstrates that AT2 cells can be delivered and retained in acellular lung scaffolds; thus with preconditioning and supporting cells, may be used for re-epithelialization. Selection and characterization of appropriate cell sources for use in recellularization, will be critical for ultimate clinical application.