Establishment of three-dimensional laminated lymphatic network autografts based on adipose tissue-derived stem cells (ASCs)

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K08506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Hirosaki University
• Principal Investigator: Asano Yoshiya 弘前大学, 医学研究科, 講師 (50359494)
• Co-Investigator(Kenkyū-buntansha): 下田 浩 弘前大学, 医学研究科, 教授 (20274748)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 人工脈管組織 / 間葉系幹細胞 / リンパ管 / 血管 / リンパ浮腫

Outline of Final Research Achievements

Artificial three-dimensional vascular network tissues based on human adipose tissue-derived mesenchymal stem cells (hASCs) were constructed due to the aim of regenerative medicine for secondary lymphedema. Compared to the previous fibroblast-based cases, the promotion of vascular and lymphatic network formation was observed, and the three-dimensional hASC-based tissue was found to be more effective than the conventional fibroblast-based case in the formation of vascular network. The results suggested that the enhancement of expression of angiogenesis-related factors by hASCs was involved. Transplantation of vascular network tissue resulted in good engraftment with pericyte or smooth muscle-like differentiation of hASCs. On the other hand, transplantation of lymphatic network tissue showed regression of vascular vessels, but the results in the mouse model of lymphatic flow regeneration suggested anastomosis between deep and superficial lymphatic vessels and new channel formation.

Free Research Field

組織工学による再生医療

Academic Significance and Societal Importance of the Research Achievements

本研究により、自己由来細胞として低侵襲で採取可能なhASCを用いた人工脈管網組織が移植可能であり、血管網組織については機能的な微小血管床が形成されることを示した。また、リンパ管網組織は脈管の生着は限定的だが、欠損したリンパ管網の吻合に寄与することが示唆され、従来の手法に比べてより有効な治療法を提供しうると考えられる。また、細胞凍結技術を融合した迅速な人工脈管組織構築技術を開発した。これらは、脈管形成過程の基礎研究ならびに脈管組織の再生医療研究に寄与しうる成果である。