Challenges to rejuvenate aged-cardiac stem cells by genome editing to develop next generation therapeutic strategies for heart failure.

• Project/Area Number: 15K15508
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular surgery
• Research Institution: Yamaguchi University
• Principal Investigator: HAMANO Kimikazu 山口大学, 医学(系)研究科(研究院), 教授 (60263787)
• Co-Investigator(Kenkyū-buntansha): 細山 徹 山口大学, 医学(系)研究科(研究院), 助教 (20638803)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 心筋幹細胞 / 幹細胞老化 / 心不全 / 細胞移植療法 / 加齢 / 細胞老化

Outline of Final Research Achievements

In recent years, it has been pointed out the possibility of “aging” in elderly patients-derived cardiac stem cells, leading to take measures against stem cell therapy for elderly patients with severe heart failure. In this study, we aimed to clarify the correlation of stem cell aging with patient’s age and to develop novel strategies to induce rejuvenation of “aged” cardiac stem cells using 26 patients-derived cardiac stem cells isolated from 2-83 years old. As a result, however, “aging” in elderly patients-derived cardiac stem cells was quite limited, meaning that it is not necessary to induce rejuvenation of elderly patient-derived cardiac stem cells. This encouraged us to use elderly patient-derived cardiac stem cells in cell-based therapy for elderly patients with severe heart failure.

Research Products

• [Journal Article] Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human cardiac stem cells. (2017)
  • Author(s): Nakamura T, Hosoyama T, Murakami J, Samura M, Ueno K, Kurazumi H, Suzuki R, Mikamo A, Hamano K.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Influence of aging on the quantity and quality of human cardiac stem cells. (2016)
  • Author(s): Nakamura T, Hosoyama T, Kawamura D, Takeuchi Y, Tanaka Y, Samura M, Ueno K, Nishimoto A, Kurazumi H, Suzuki R, Ito H, Sakata K, Mikamo A, Li TS, Hamano K.
  • Journal Title: Scientific Reports Volume: ６ Issue: 1 Pages: 22781-22781
  • DOI: 10.1038/srep22781
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Influence of Aging on Cardiac Stem/Progenitor Cells (2016)
  • Author(s): Tohru Hosoyama
  • Organizer: BIT's 7th World Gene Convention-2016
  • Place of Presentation: 中国 上海市
  • Year and Date: 2016-11-03
  • Int'l Joint Research / Invited
• [Presentation] 加齢や心機能低下がヒト心筋幹細胞(cardiosphere-derived cells)の量と質に与える影響 (2016)
  • Author(s): 中村玉美、細山 徹、竹内由利子、田中裕也、佐村 誠、上野耕司、美甘章仁、李 桃生、濱野公一
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪府大阪市・大阪国際会議場
  • Year and Date: 2016-03-17