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[101] This notwithstanding the delineation of human lung epithelial stem and progenitor cell hierarchies is beset with practical difficulties likely to slow progress. Translational studies aimed at identifying stem cell homologues of those in mice will need to consider differences in the distribution of epithelial cell lineages along the proximal-distal axis of the murine and human airway tree.[62] Murine cells also have extremely long telomeres,[102] endowing them with a far more prodigious replicative capacity than human cells. Consequently, human homologues of putative mouse lung epithelial stem cells may have BMS 777607 a more restricted proliferative potential and may not be appropriate therapeutic targets in clinical contexts. Practical issues related to the acquisition of human lung tissue biopsies suitable for stem cell experimentation will impact the development and refinement of optimal strategies for stem cell isolation and characterization. The modelling of lung epithelial stem cell organization and regulation will require access to normal lung tissue from different anatomical Neratinib regions along the proximal-distal axis of the airway tree and its processing in a timely manner. Regular access to normal lung is rare, and resected ��normal�� lung tissue and bronchoscopy samples are invariably acquired from patients undergoing procedures for diverse clinical indications. These clinical indications are likely to affect the biomarker profile and attributes of putative stem and progenitor cells, and also amplify the intrinsic biological RVX-208 variability of measured human parameters necessitating larger sample sizes for statistical validation of stem cell attributes. That said, recent clinical studies demonstrating the therapeutic efficacy of tracheobronchial reconstruction using bioengineered recellularized human tracheal matrix scaffolds[103] are a cause for optimism for the future of stem cell-based therapies in lung regenerative medicine. The authors are supported by grants from the Australian National Health and Medical Research Council (Grant 1009374) and the Victorian Cancer Agency. ""5048" "Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of ��herbal high�� preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown.