Tissue regeneration based on modulation of macrophage phenotypes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K12091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Toita Riki 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (40611554)
• Co-Investigator(Kenkyū-buntansha): 姜 貞勲 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (50423512)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: マクロファージ / 組織修復 / ナノメディシン / 褥瘡 / 骨 / チタン / 老化 / 炎症

Outline of Final Research Achievements

Macrophages (Mf) play a central role in restoring tissue homeostasis by controlling inflammation and tissue repair. They are broadly divided into M1 and M2types. Following tissue injury, circulating monocytes are quickly recruited to the injury and differentiate into M1 type Mf, which produce pro-inflammatory mediators and ROS to kill invading pathogens. These M1 Mf then polarize into M2 Mf, which mediate inflammation resolution and tissue repair by producing anti-inflammatory cytokines and growth factors. We demonstrate that nanoparticles-mediated M1-to-M2 polarization has beneficial effects on tissue repair. This is the first report of a simple, safe nanomedicine-induced M2-like Mf polarization that promotes the tissue repair of subcutaneous tissue and bone in young and middle-aged mice, suggesting that dysfunctional macrophages are a potential clinical target for overcoming impaired tissue repair in elderly individuals.

Free Research Field

バイオマテリアル

Academic Significance and Societal Importance of the Research Achievements

マクロファージの表現型を活用し疾患治療や組織再生を促す戦略は、十分に研究が進んでいなかった。本研究では、ナノ粒子によりM1型からM2型にスイッチングする技術基盤を確立し、皮膚虚血再灌流モデル（褥瘡）および骨傷害モデルにおいても、ナノ粒子がマクロファージ表現型のスイッチング効果を示すとともに、それにより幹細胞や前駆細胞を含む周辺細胞に影響を与え、組織修復が促進できることを明らかにした。このナノ粒子によりマクロファージ表現型のスイッチング戦略は、将来的に再生治療や炎症性疾患治療への応用が期待される。