2022 Fiscal Year Final Research Report

Novel cell therapy for pulmonary hypertension and pulmonary ischemia-reperfusion injury

Research Project

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Project/Area Number	20K09140
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55030:Cardiovascular surgery-related
Research Institution	Tohoku University
Principal Investigator	MATSUO Satoshi 東北大学, 医学系研究科, 大学院非常勤講師 (10869655)
Co-Investigator(Kenkyū-buntansha)	齋木佳克東北大学, 医学系研究科, 教授 (50372298) 正木直樹東北大学, 医学系研究科, 大学院非常勤講師 (00837403) 鈴木佑輔東北大学, 医学系研究科, 助教 (70791698) 細山勝寛東北大学, 医学系研究科, 大学院非常勤講師 (70837046)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	肺高血圧 / 肺虚血再灌流障害 / 再生医療
Outline of Final Research Achievements	We established a rat model of pulmonary hypertension following a previously described method. Subcutaneous injection of monocrotaline into the rat's neck induced pulmonary hypertension after a 3-week period. Cardiac catheterization was subsequently performed to measure right ventricular systolic pressure, confirming an increase in pressure and the presence of pulmonary hypertension. To further enhance our understanding of pulmonary hypertension, we aimed to create a novel rat model by inducing ischemia-reperfusion injury through pulmonary artery clamping in the existing monocrotaline-induced pulmonary hypertension model. The development of a long-term survival animal model is crucial to verify the therapeutic efficacy of stem cells and elucidate the underlying treatment mechanisms. Therefore, our objective was to establish an animal model capable of maintaining pulmonary hypertension for an extended duration. We optimized the monocrotaline dosage to refine the animal model accordingly.
Free Research Field	心臓血管外科学
Academic Significance and Societal Importance of the Research Achievements	これまで肺高血圧動物モデルに対する骨髄間葉系幹細胞移植の研究は報告されているが、これらの報告は血管内皮細胞の抗アポトーシス効果や血管平滑筋の異常増殖制御が主な治療機序とされており、投与細胞が血管内皮細胞に分化し、肺高血圧を改善させる治療機序の報告はない。また、肺高血圧下の肺に対する虚血再灌流障害の予防を髄間葉系幹細胞移植にて検討した研究もない。そのため、本研究でMuse細胞の効果が証明されれば、腫瘍化のない幹細胞移植が肺高血圧治療および虚血再灌流障害の予防に対して、今後臨床応用されるきっかけとなる研究と確信している。