干细胞前临床评估:干细胞来源于Wharton's jelly的干细胞在干扰素-γ刺激下进行了评估。
Preclinical Evaluation of interferon-gamma primed human Wharton's jelly-derived mesenchymal stem cells.
发表日期:2023
作者:
Sang-Jin Park, Dae Seong Kim, Myeongjin Choi, Kang-Hyun Han, Ji-Seok Han, Keon Hee Yoo, Kyoung-Sik Moon
来源:
Stem Cell Research & Therapy
摘要:
人类间充质干细胞(MSCs)在许多免疫介导的疾病中作为细胞疗法的潜力一直受到研究。MSCs被认为是治疗顽固疾病最有前途的细胞治疗药物之一。最近,已经研究了预处理MSCs的方法,从而产生了具有增强临床应用潜力的细胞产品。干扰素γ(IFN-γ)预处理是目前一种用于增加MSCs治疗效力的方法。本研究确定了用于BALB/c-nu/nu雄性和雌性小鼠的IFN-γ预处理Wharton’s Jelly来源(WJ)MSC的全身毒性,肿瘤形成和生物分布。在多次剂量研究中,接受5×106个细胞/kg IFN-γ预处理MSC处理的小鼠未出现死亡或病理性病变。在肿瘤形成研究中,经皮下注射处理的小鼠中,一只示出肺支气管肺泡腺瘤,但对人特异性抗线粒体抗体检测为阴性,提示腺瘤为自发的小鼠起源。实时定量聚合酶链反应的生物分布研究表明,在28天内,IFN-γ预处理的MSC经全身清除。根据毒性,生物分布和肿瘤形成研究的结论,我们得出结论:在5×106个细胞/kg的剂量下,IFN-γ预处理的MSCs不会引起肿瘤形成和不良变化。
The potential of human mesenchymal stem cells (MSCs) for cell therapy has been investigated in numerous immune-mediated conditions; MSCs are considered one of the most promising cellular therapeutics to treat intractable diseases. Recently, approaches to prime MSCs have been investigated, thereby generating cellular products with enhanced potential for a variety of clinical applications. Interferon-gamma (IFN-γ) priming is a current approach used to increase the therapeutic efficacy of MSCs. In this study, we determined the systemic toxicity, tumorigenicity and biodistribution of IFN-γ-primed Wharton's jelly-derived (WJ)-MSCs in male and female BALB/c-nu/nu mice. There were no deaths or pathologic lesions in the mice treated with 5 × 106 cells/kg IFN-γ-primed MSCs in the repeated dose study. In the tumorigenicity study, one of the subcutaneously treated mice showed bronchioloalveolar adenoma in the lung but tested negative for human-specific anti-mitochondrial antibody, suggesting the spontaneous murine origin of the adenoma. A biodistribution study using real-time quantitative polymerase chain reaction demonstrated the systemic IFN-γ-primed MSC clearance by day 28. Based on the toxicity, biodistribution, and tumorigenicity studies, we concluded that IFN-γ-primed MSCs at 5 × 106 cells/kg do not induce tumor formation and adverse changes.