Transplantation of Airway Epithelial Stem/Progenitor Cells: A Future for Cell-Based Therapy
Transplantation of Airway Epithelial Stem/Progenitor Cells: A Future for Cell-Based Therapy
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DOI：
10.1165/rcmb.2016-0181ma
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发表时间：
2017-01-01
影响因子：
6.4
通讯作者：
Reynolds, Susan D.
中科院分区：
文献类型：
--
作者：
Ghosh, Moumita;Ahmad, Shama;Reynolds, Susan D.
细胞疗法有可能通过替换功能不全的细胞来治愈疾病。尽管组织干细胞(TSC)被认为是最理想的治疗细胞，但TSC/祖细胞混合移植拯救了生命。我们之前纯化了小鼠气管、支气管上皮TSCs，并报道了在体外扩增产生了大量TSCs。然而，这些培养物中也含有TSC来源的祖细胞，用流式细胞仪重新纯化TSC会影响TSC的自我更新。这些局限性促使我们确定ATSC/祖细胞混合物是否会重新填充受损的呼吸道上皮。我们开发了一种细胞移植方案，并证明了移植的小鼠和人气管支气管上皮TSC/祖细胞混合物占呼吸道上皮细胞的20%-25%，积极促进上皮修复，并持续至少43天。移植后2周，TSCs/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。我们的结论是，使用成人气管、支气管TSCs/祖细胞进行细胞治疗是一种有效的治疗选择。
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 aTSC/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.