Lung regeneration using adipose tissue-derived stem cells~Differentiation into alveolar epithelial cells and development of stem cells therapy~

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16417
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Osaka University
• Principal Investigator: Fukui Eriko 大阪大学, 医学系研究科, 助教 (90814591)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 脂肪組織由来幹細胞 / 慢性閉塞性肺疾患 / 細胞移植治療 / 肺胞上皮細胞 / 肺再生

Outline of Final Research Achievements

Chronic obstructive pulmonary disease is a leading cause of mortality globally, with no effective therapy yet established. Whether adipose tissue-derived stem cells (ADSCs) differentiate into functional cells remains uncertain, and no study has reported on the mechanism by which ADSCs improve lung functionality. Thus, in this study, we examined whether ADSCs differentiate into lung alveolar cells and are able to ameliorate lung injury caused by elastase-induced emphysema in model mice. Here, we induced ADSCs to differentiate into type 2 alveolar epithelial cells in vitro. We demonstrated that ADSCs can differentiate into type 2 alveolar epithelial cells in an elastase-induced emphysematous lung and that ADSCs improve pulmonary function of emphysema model mice, as determined with spirometry and 129Xe MRI. These data revealed a novel function for ADSCs in promoting repair of the damaged lung by direct differentiation into alveolar epithelial cells.

Free Research Field

呼吸器外科

Academic Significance and Societal Importance of the Research Achievements

慢性閉塞性肺疾患 (COPD)などの難治性呼吸器疾患は年々著しく増加している。肺移植以外の根治的な治療法は確立されておらず、予後不良であり、新たな治療法の開発が喫緊の課題である。現在の幹細胞治療ではパラクラン効果が主な作用であり、このような非可逆的な肺胞破壊を伴う難治性呼吸器疾患に対しては治療効果に限界がある。本研究では幹細胞自身が肺胞細胞へ分化する可能性を示し、COPDに対する根治的な肺胞再生治療の可能性を示した。