A novel treatment for perinatal chronic lung disease using mesenchymal stem cells stably transduced with a dominant-negative inhibitor of CCL2.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15667
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nagoya University
• Principal Investigator: Suzuki Toshihiko 名古屋大学, 医学部附属病院, 病院助教 (60711083)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 再生医療 / 新生児慢性肺疾患 / 7ND / CCL2

Outline of Final Research Achievements

7ND-MSC is a mesenchymal stem cell introduced a mutant (7ND) of human CCL2 protein that functions as a potent antagonist of CCL2, that is a monocyte-activating factor. In this study, we administered 7ND-MSC, control MSC or Ringer's acetate solution to neonatal chronic lung disease (CLD) model rats and evaluated their therapeutic effects. The 7ND-MSC-treated group showed the significant improvement of hyperoxia-induced lung pathology and secondary pulmonary hypertension, compared with the control MSC-treated group. Furthermore, compared with MSC alone, 7ND-MSC decreased alveolar macrophages, particularly inflammatory (M1) macrophages, and suppressed the mRNA expression levels of IL-6 and CCL2 in lung tissue. Thus, the effects of 7ND-MSCs is considered to be due to 7ND enhancing the anti-inflammatory effect.

Free Research Field

小児科

Academic Significance and Societal Importance of the Research Achievements

間葉系幹細胞（MSC）は様々な疾患に対し臨床応用されており、その効果および安全性が確認されている。7ND-MSCは、マクロファージの遊走及び活性化を強く促すケモカイン、CCL2を阻害する作用を持つ7NDを遺伝子導入したMSCである。そのため、新生児慢性肺疾患（CLD）モデル動物に対する7ND-MSC投与は、MSCによる細胞療法の治療効果に加え、7NDの抗マクロファージ作用により、さらに高い治療効果が期待される。本研究にて高い有効性および安全性が確認されれば、ヒトへの臨床応用も可能と考えられ、CLD児の呼吸器学的予後および神経学的予後の向上に大きく寄与すると思われる。