Elucidation of the immunomodulatory mechanism of bone marrow mesenchymal stem cell therapy for the development of new neurological disease treatments

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16554
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Yokokawa Kazuki 札幌医科大学, 医学部, 助教 (30781273)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 間葉系幹細胞 / アルツハイマー病 / 多発性硬化症 / βアミロイド

Outline of Final Research Achievements

We reported the usefulness of bone marrow mesenchymal stem cell (BMSC) therapy in Alzheimer's disease (AD) model mice, and showed that β-amyloid phagocytosis was promoted through upregulation of CD14 in microglia. In this study, we aimed to examine the details of the therapeutic mechanism. In addition, we tried BMSC treatment in models such as amyotrophic lateral sclerosis and multiple sclerosis (MS), and aimed to examine the therapeutic mechanism through peripheral blood lymphocyte analysis. We showed that BMSC treatment promoted ApoE expression in AD model mouse brains and in vitro microglial cell lines. We attempted to create an autoimmune encephalomyelitis model as an MS model, but we were unable to create a stable model.

Free Research Field

脳神経内科

Academic Significance and Societal Importance of the Research Achievements

BMSCはGVHD・脊髄損傷・脳梗塞などで臨床使用が開始されており、本学はBMSC治療のノウハウや品質管理・安全性の面で実績がある。神経疾患に関しては筋萎縮性側索硬化症患者への臨床治験も進めている。本研究の成果により神経変性疾患における疾患修飾作用のメカニズムの一つを明らかにし、臨床応用へさらに近づいたものと考える。