autologous transplantation of adipose tissue derived mesenchymal stromal cells to the old myocardial infarction heart

• Project/Area Number: 18K15839
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Chiba University
• Principal Investigator: kondo naomichi 千葉大学, 医学部附属病院, 医員 (70797000)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 心筋再生 / 脂肪間葉系幹細胞 / 心筋梗塞 / 心外膜 / 細胞移植 / 間葉系幹細胞

Outline of Final Research Achievements

Assuming that the most effective cell transplantation (TX) method is autologous TX without immune rejection, we established an autologous TX model by transplanting adipose-derived mesenchymal stem cells into the pericardial space of mice with myocardial infarction. The TX treatment effect was compared with conventional syngeneic and allogeneic TX models.

The autologous TX group showed the most prolonged graft survival. Lymphocytic infiltration into the graft was lowest in the autologous TX group and highest in the allogeneic TX group. Echocardiography showed the autologous TX prevented cardiac enlargement. Adipose-derived mesenchymal stem cells could proliferate and differentiate into self-beating myocytes and vascular endothelial cells on culture dishes after being frozen and thawed on culture dishes.

Academic Significance and Societal Importance of the Research Achievements

心臓領域における従来の細胞移植研究では、細胞移植効果は実臨床レベルでは不明である。その原因だが、我々は移植した細胞が免疫拒絶され長期生着しない問題に着目した。脂肪由来間葉系幹細胞は自己の脂肪組織から採取可能であり、安全性、倫理性に優れ最も実用的な移植細胞ソースである。それを用いたマウス自家移植モデルを確立することによって、自家移植が免疫拒絶反応を軽減し移植片を長期生着させることを確認した。また心筋内に細胞を針で注射することなく心外膜で心嚢腔内に移植片を覆い封じ込めることにより、非侵襲的な細胞移植方法も同時に確立した。

Research Products

• [Presentation] Transplantation of Adipose-Derived Stromal Cells with Self-Assembling Peptide Scaffolds into the Pericardial Space Prevents Cardiac Remodeling after Myocardial Infarction (2020)
  • Author(s): Kondo N, Nagai T, Aoki I, Kanda M, Takahashi T, Kobayashi Y.
  • Organizer: 日本循環器学会
• [Presentation] Pericardial transplantation of adipose-derived stromal cells with self-assembling peptides scaffold prevents cardiac remodeling after myocardial infarction in mice (2019)
  • Author(s): Kondo N, Nagai T, Aoki I, Takahashi T, Kanda M, Kobayashi Y
  • Organizer: Europiean Society of Cardiology
  • Int'l Joint Research
• [Presentation] Transplantation of Brown Adipose Tissue-Derived Cells with the Self-Assembling Peptides Scaffold into the Pericardial Space Attenuates Cardiac Remodeling in a Mouse Old Myocardial Infarction Model (2018)
  • Author(s): Kondo N
  • Organizer: American Heart Association 2018 Scientific Session
  • Int'l Joint Research