Yang Ji Won, Seo Yoojin, Shin Tae-Hoon, Ahn Ji-Su, Oh Su-Jeong, Shin Ye Young, Kang Min-Jung, Lee Byung-Chul, Lee Seunghee, Kang Kyung-Sun, Hur Jin, Kim Yeon-Soo, Kim Tae-Yoon, Kim Hyung-Sik
Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan 50612, Korea.
Dental and Life Science Institute, Pusan National University, Yangsan 50612, Korea.
Antioxidants (Basel). 2020 Nov 23;9(11):1165. doi: 10.3390/antiox9111165.
The immunoregulatory abilities of mesenchymal stem cells (MSCs) have been investigated in various autoimmune and allergic diseases. However, the therapeutic benefits observed in preclinical settings have not been reproducible in clinical trials. This discrepancy is due to insufficient efficacy of MSCs in harsh microenvironments, as well as batch-dependent variability in potency. Therefore, to achieve more beneficial and uniform outcomes, novel strategies are required to potentiate the therapeutic effect of MSCs. One of simple strategies to augment cellular function is genetic manipulation. Several studies showed that transduction of antioxidant enzyme into cells can increase anti-inflammatory effects. Therefore, we evaluated the immunoregulatory abilities of MSCs introduced with extracellular superoxide dismutase 3 (SOD3) in the present study. SOD3-overexpressed MSCs (SOD3-MSCs) reduced the symptoms of murine model of atopic dermatitis (AD)-like inflammation, as well as the differentiation and activation of various immune cells involved in AD progression. Interestingly, extracellular vesicles (EVs) isolated from SOD3-MSCs delivered SOD3 protein. EVs carrying SOD3 also exerted improved therapeutic efficacy, as observed in their parent cells. These results suggest that MSCs transduced with SOD3, an antioxidant enzyme, as well as EVs isolated from modified cells, might be developed as a promising cell-based therapeutics for inflammatory disorders.
间充质干细胞（MSCs）的免疫调节能力已在各种自身免疫性和过敏性疾病中得到研究。然而，临床前研究中观察到的治疗益处并未在临床试验中得到重现。这种差异是由于MSCs在恶劣微环境中的疗效不足，以及效力的批次依赖性变异性所致。因此，为了获得更有益和一致的结果，需要新的策略来增强MSCs的治疗效果。增强细胞功能的一种简单策略是基因操作。多项研究表明，将抗氧化酶转导到细胞中可增加抗炎作用。因此，在本研究中，我们评估了导入细胞外超氧化物歧化酶3（SOD3）的MSCs的免疫调节能力。过表达SOD3的MSCs（SOD3-MSCs）减轻了特应性皮炎（AD）样炎症小鼠模型的症状，以及参与AD进展的各种免疫细胞的分化和活化。有趣的是，从SOD3-MSCs分离的细胞外囊泡（EVs）传递了SOD3蛋白。携带SOD3的EVs也表现出改善的治疗效果，正如在其亲代细胞中观察到的那样。这些结果表明，用抗氧化酶SOD3转导的MSCs以及从修饰细胞中分离的EVs，可能被开发成为一种有前途的用于炎症性疾病的细胞疗法。
