Development of Motor Improvement and Novel Therapies through Functional Mesodermal Organoid Transplantation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03328
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: Juntendo University
• Principal Investigator: Akazawa Chihiro 順天堂大学, 大学院医学研究科, 教授 (80291160)
• Co-Investigator(Kenkyū-buntansha): 久松 大介 順天堂大学, 大学院医学研究科, 特任研究員 (20880272) ; 馬渕 洋 藤田医科大学, 医学部, 准教授 (50424172) ; 奈良岡 佑南 順天堂大学, 大学院医学研究科, 博士研究員 (50828522)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: オルガノイド / 三次元培養 / 炎症性疾患

Outline of Final Research Achievements

In this study, we aimed to characterize CD73+ cells by comparing them with conventional heterogeneous MSCs and to determine the appropriate transplantation route and cell form for CD73+ cells in a mouse model of DSS-induced colitis. mRNA sequencing analysis showed that CD73+ cells exhibited a down-regulation of inflammatory gene expression and an upregulation of extracellular matrix-related gene expression. Furthermore, three-dimensional CD73+ cell spheroids showed enhanced engraftment at the injured site through the enteral route, facilitated extracellular matrix remodeling, and downregulated inflammatory gene expression in fibroblasts, attenuating colonic atrophy. Our results highlight that the transplantation of homogeneous cell populations with well-characterized properties is beneficial for inflammatory bowel disease treatment.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、均一なCD73+細胞集団の特徴に基づいた適切な移植方法を示し、大腸炎抑制の基礎となるメカニズムの一つとして、移植細胞と組織常在線維芽細胞との相互作用を明らかにした。本成果は、潰瘍性大腸炎やその他の炎症に基づく疾患の新たな治療法となり得る。さらに、MSCsの臨床応用において、移植細胞や分泌因子の供給源としてCD73+細胞スフェロイドが有用である可能性を示唆している。