Development of novel therapeutic strategies for cartilage defects based on molecular mechanisms of hyaline cartilage regeneration promoted by chondrocyte sheets.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07297
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Tokai University
• Principal Investigator: TOYODA Eriko 東海大学, 医学部, 特任准教授 (90749269)
• Co-Investigator(Kenkyū-buntansha): 佐藤 正人 東海大学, 医学部, 教授 (10056335)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 再生医療 / 細胞シート工学 / 硝子軟骨 / 軟骨分化

Outline of Final Research Achievements

Chondrocytes obtained from juvenile polydactyly patients (PD cells) are a promising allogeneic cell source for cartilage regeneration．PD sheets, that fabricated from PD cells, have demonstrated hyaline cartilage regeneration in rat and rabbit xenogeneic osteochondral defect model and patients with osteoarthritis in clinical trial. So far, protein factors secreted from PD sheets are thought to contribute to the hyaline cartilage regeneration. We had identified some proteins that their amount of secretion correlated with the efficacy of PD sheets. To clarify the function of these factors in the hyaline cartilage regeneration, we analyzed mode of action of 4 protein factors on chondrogenic differentiation of PD cells and effect on cell properties during PD sheet fabrication.
Our results suggests that factor A can promoted chondrogenic redifferentiation, support the proliferation of PD cells and be involved in the maintenance of chondrogenic potential during fabrication of PD sheets.

Free Research Field

運動器疾患の再生医療および 軟骨損傷治療薬の開発

Academic Significance and Societal Importance of the Research Achievements

軟骨が損傷し痛みを生じる変形性膝関節症の罹患率は高く、高齢者の健康寿命を縮める要因となっており、低侵襲の治療法開発が喫緊の課題である。しかし、変形性膝関節症をはじめとする軟骨損傷に対する修復効果が実証され、臨床応用された薬剤はない。
細胞シートによる関節軟骨再生では、硝子軟骨による再生が得られており、この作用機序を模倣し硝子軟骨再生に関わる因子を薬剤として応用することで変形性膝関節症の軟骨欠損に対しても有効な新規治療法につながる可能性がある。本研究は、同定された硝子軟骨再生にかかわる因子の作用機序を応用した軟骨再生促進薬の開発に寄与するものである。