Ghosh Moumita, Ahmad Shama, White Carl W, Reynolds Susan D
1 Department of Pediatrics, National Jewish Health, Denver, Colorado.
2 Department of Anaesthesiology and Perioperative Medicine, University of Alabama, Birmingham, Alabama.
Am J Respir Cell Mol Biol. 2017 Jan;56(1):1-10. doi: 10.1165/rcmb.2016-0181MA.
Cell therapy has the potential to cure disease through replacement of malfunctioning cells. Although the tissue stem cell (TSC) is thought to be the optimal therapeutic cell, transplantation of TSC/progenitor cell mixtures has saved lives. We previously purified the mouse tracheobronchial epithelial TSCs and reported that in vitro amplification generated numerous TSCs. However, these cultures also contained TSC-derived progenitor cells and TSC repurification by flow cytometry compromised TSC self-renewal. These limitations prompted us to determine if a TSC/progenitor cell mixture would repopulate the injured airway epithelium. We developed a cell transplantation protocol and demonstrate that transplanted mouse and human tracheobronchial epithelial TSC/progenitor cell mixtures are 20-25% of airway epithelial cells, actively contribute to epithelial repair, and persist for at least 43 days. At 2 weeks after transplantation, TSCs/progenitor cells differentiated into the three major epithelial cell types: basal, secretory, and ciliated. We conclude that cell therapy that uses adult tracheobronchial TSCs/progenitor cells is an effective therapeutic option.
细胞疗法有通过替换功能异常的细胞来治愈疾病的潜力。尽管组织干细胞（TSC）被认为是最佳的治疗细胞，但TSC/祖细胞混合物的移植已挽救了生命。我们之前纯化了小鼠气管支气管上皮TSC，并报道体外扩增产生了大量TSC。然而，这些培养物中也含有TSC来源的祖细胞，并且通过流式细胞术对TSC进行再纯化会损害TSC的自我更新能力。这些局限性促使我们去确定TSC/祖细胞混合物是否能重新填充受损的气道上皮。我们制定了一种细胞移植方案，并证明移植的小鼠和人气管支气管上皮TSC/祖细胞混合物占气道上皮细胞的20% - 25%，积极参与上皮修复，并持续至少43天。移植后2周，TSC/祖细胞分化为三种主要的上皮细胞类型：基底细胞、分泌细胞和纤毛细胞。我们得出结论，使用成人气管支气管TSC/祖细胞的细胞疗法是一种有效的治疗选择。
