2005 Fiscal Year Final Research Report Summary
Analysis of lung stem cells dynamics and homing mechanisms under inflammatory lung diseases
| Project/Area Number |
16590760
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
FUJISHIMA Seitaro Keio University, school of medicine, department of emergency and critical care, assistant professor, 医学部, 講師 (00173419)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Fumitake Keio University, school of medicine, department of emergency and critical care, adjunct, 医学部, 助手 (30338040)
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| Project Period (FY) |
2004 – 2005
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| Keywords | stem cell / radiation pneumonitis / acute lung injury / side population cell / Musashi-1 |
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| Research Abstract |
1.Expression of lung stem cell markers and the analysis of mediators involved in the homing of stem cells :
1)Mice acid aspiration model : We treated mice with various concentrations and volumes of hydrochloric acid, and examined pathological changes. We found that 0.5 M is the best concentration for this model, since pulmonary edema was reproducibly examined.
We next examined the expression of Musashi-1, a marker of epithelial stem cells, to elucidate the dynamic regulation of lung stem cells after acute lung injury. As a result, we found an increase in Musashi-1 positive cells around bronchi after acid inhalation. Since Musashi-1 is known for its epithelial expression in various tissues, we speculated that lung stem cells may be involved in tissue repair and regeneration after acid injury.
2)Rat radiation pneumonitis/fibrosis model : We fond an increased expression of MDC and TARC in lung tissue, and started to examine their involvement in stem cell recruitment.
3)Mice burn-primed endotoxemia model : We found a significant increase in lung MDC, TARC in burned mice, and are in the process of examining the effect of CCR4 antagonist.
2.Establishing the protocol to stably collect lung side population (SP) cells and quantifying lung SP cells by this method :
To establish the protocol to separate SP cells from lung tissue, we tried various methods of lung homogenation, various kinds and concentrations of enzymes, conditions of incubation, etc. Since the yields of SP cells varied and were very low (0.05〜0.8%), we could not detect the changes in lung SP cells after lung injury by this method. However, the existence of lung stem cells was also suggested by this method.
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