Abstract
摘要:我們在之前的研究已經找到一群 SSEA-1+的肺部幹細胞,而且利用這群肺部幹細胞應用到呼吸道過敏性發炎疾病的治療,得到相當不錯的治療結果,而且發現可能與Clara 細胞分泌蛋白(Clara cell secretory protein, CCSP)有關。但是,我們在研究這群細胞時主要是由新生小鼠的肺部分離,因此取得較為不容易,而且似乎還可以加以分群。此外,我們也想由這群幹細胞看是否能夠再加以分群。我們在此一計畫中也要找出與肺部幹細胞分化有關的轉訊因子(transcription factors),看是否能夠利用這些轉訊因子的基因來讓肺部上皮細胞轉成肺部幹細胞。同時,也要瞭解是否能夠利用SSEA-1 分子來讓多潛力幹細胞和胚胎幹細胞分化成肺部幹細胞。此外,我們也要建立肺部發炎反應的動物模式,以了解這些肺部幹細胞是否具有組織修補和免疫調控的能力。第一年:我們之前已經建立肺部幹細胞的培養,尤其是SSEA-1 陽性的肺部幹細胞,並證明其具有分化和免疫調控的能力。但是,我們在之前的研究中也發現如果使用CD133 來進行染色,可以發現SSEA-1 陽性的這群細胞實際上有兩群細胞。因此,我們要進一步分析這兩群細胞是否有不同的分化能力和免疫調控上的差別。第二年:在第二年的計畫中,我們將進一步研究是否可以找到關鍵的轉訊因子基因,利用這些特定的轉訊因子基因可以讓肺部上皮細胞轉化成幹細胞。主要的原因是我們在之前的實驗中是由新生小鼠的肺部直接培養出肺部幹細胞,但是每次實驗就需要相當數目的新生小鼠,而且無法大量增殖。所以,如果找到轉訊因子能夠讓肺部上皮細胞轉成具有幹細胞能力,就可以能夠較方便地培養出未來能夠應用的肺部幹細胞。此外,我們也將嘗試看看是否可以由SSEA-1 此一分子來當作一個報告因子,由誘發性多潛能幹細胞(iPSC)或是胚胎幹細胞來誘發出具有肺部幹細胞特性的幹細胞。第三年:如果我們能夠由肺部上皮細胞或是iPSC 培養出肺部幹細胞,我們將進一步由建立好的發炎性肺部疾病來了解這些誘發出來的肺部幹細胞,是否具有分化和免疫調節的能力。我們將分別利用建立好的呼吸道過敏疾病和呼吸道受傷的疾病,利用這些由肺部上皮細胞或是iPSC 培養出來的肺部幹細胞來進行治療,以了解這些肺部幹細胞是否具有組織修補和免疫調控的能力。我們目前對肺部幹細胞的了解並不是特別清楚,所以進一步研究這些肺部幹細胞,再加以應用到肺部疾病的治療上。尤其是可以利用此一研究計畫來找出相關的轉訊因子,來利用肺部上皮細胞來分化成幹細胞。還有,利用iPSC 或是胚胎幹細胞來誘導成肺部幹細胞。我們將進一步利用已經建立好的動物模式,來研究這些肺部幹細胞是否具有組織修補和免疫調控的能力。
Abstract: In this project, we plan to investigate the subpopulations of SSEA-1+ lung stem/progenitor cells toclarify their differentiation ability. In addition, we also like to identify the transcription factorsinvolved in the development of lung stem/progenitor cells. We will like to transfect lung epithelialcells with these transcription factors to see if we could induce lung stem/progenitor cells. In addition,we also like to investigate if the SSEA-1 gene could be used to induce lung stem cells from inducedpluripotent stem cells (iPSCs) or embryonic stem (ES) cells. Further, we also like to elucidate if theselung stem/progenitor cells could exert the immune regulatory and tissue repair ability on theinflammatory lung diseases.First year: We like to further characterize the subpopulation of SSEA-1+ lung stem/progenitor cells.In our previous study, we have isolated SSEA-1+ lung stem cells and demonstrated their ability todifferentiate into type 1 and type 2 pneumocytes and tracheal epithelial cells. In addition, we havefound that the staining of CD133 could show two subpopulations of lung stem/progenitor cells. Welike to elucidate if we could further define the different subpopulations of lung stem cells for thefuture characterization.Second year: In addition, we like to identify the transcription factors important for the developmentand differentiation of lung stem/progenitor cells. We will identify the transcription factors to inducelung epithelial cells into lung stem/progenitor cells for the further development of lung stem cells. Inaddition, we also like to find out if we could use SSEA-1 as the marker to derive induced pluripotentstem cells (iPSC) or embryonic stem (ES) cells to develop into lung stem cells.Third year: We plan to investigate if pulmonary stem cells could be derived from inducedpluripotent stem cells or embryonic stem cells. We will like to investigate the effect of these lungstem/progenitor cells on the tissue repair and immune regulation of lung inflammatory diseases andinjury. We will establish the animal model of lung allergic inflammatory diseases and lung injury forthe study on the differentiation and functions of lung stem/progenitor cells.In this project, we like to study the characterization of SSEA-1+ lung stem/progenitor cellssubpopulation. Especially, we like to further characterize the effector genes and molecules involvedin the functions of these lung stem/progenitor cells. We also like to identify the transcription factorsinvolved in the development of lung stem/progenitor cells to induce the lung epithelial cells into lungstem cells. Further, we also like to study if we could induce the iPSCs or ES cells into lungstem/progenitor cells. We also like to investigate the effects of all these stem cells on tissue repair andimmune regulation on lung inflammatory diseases and injury.
Keyword(s)
氣喘
肺部幹細胞
免疫調節
Pulmonary stem cells
inflammatory lung disease
transcription factors