Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids

大鼠胎肺植入促进肺再生及皮质类固醇促进肺泡干细胞分化

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作者:Daisuke Matsumoto, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Shinichi Sakamoto, Mika Takashima, Naoya Kawakita, Hiromitsu Takizawa

Conclusions

Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.

Methods

Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups.

Results

The grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. Conclusions: Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.

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