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High Dose of Intravenous Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells (CLV-100) Infusion Displays Better Immunomodulatory Effect among Healthy Volunteers: A Phase 1 Clinical Study
Stem Cells International ( IF 4.3 ) Pub Date : 2020-09-28 , DOI: 10.1155/2020/8877003
Sze-Piaw Chin 1, 2 , Mohd-Yusoff Mohd-Shahrizal 2 , Mohd-Zuhar Liyana 2 , Kong Yong Then 2 , Soon Keng Cheong 2, 3
Affiliation  

Background. Mesenchymal stem cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord-derived MSCs (UCMSCs) are particularly attractive as an off-the-shelf allogeneic treatment in emergency medical conditions. We aim to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methodology. Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents, and grandparents) were screened for genetic mutations, infections, cancers, and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 and followed up for 6 months. We measured cytokines using ELISA including anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1RA), interleukin 10 (IL-10), pro-/anti-inflammatory cytokine interleukin 6 (IL-6), and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Results. 11 healthy subjects (LD, ; HD, ; mean age of years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA ( vs. ; ) and IL-10 ( vs. L; ); and lower levels of proinflammatory marker TNF-α ( vs. ; ) compared to LD group. Conclusion. Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.

中文翻译:

高剂量静脉注射异基因脐带来源间充质干细胞 (CLV-100) 在健康志愿者中显示出更好的免疫调节作用:1 期临床研究

背景。间充质干细胞 (MSCs) 表达刺激修复和控制免疫反应的生长因子和其他细胞因子。MSCs 还具有免疫特权,排斥风险低。脐带源性间充质干细胞 (UCMSCs) 作为紧急医疗条件下的现成同种异体治疗特别有吸引力。我们的目标是确定 Cytopeutics®(马来西亚雪兰莪)在健康志愿者中静脉输注 UCMSCs (CLV-100) 的安全性和有效性,并确定观察到免疫调节作用的有效剂量。方法. 经父母双方书面同意,在分娩足月健康婴儿后采集脐带样本。对所有 3 代人(新生儿、父母和祖父母)进行基因突变、感染、癌症和其他遗传疾病的筛查。样品被转移到经过认证的良好生产规范实验室进行处理。受试者被注入低剂量(LD,6500 万个细胞)或高剂量(HD,1.3 亿个细胞)的 CLV-100,并随访 6 个月。我们使用 ELISA 测量细胞因子,包括抗炎细胞因子白细胞介素 1 受体拮抗剂 (IL-1RA)、白细胞介素 10 (IL-10)、促/抗炎细胞因子白细胞介素 6 (IL-6) 和促炎细胞因子肿瘤坏死因子-α (TNF )。结果. 11名健康受试者(LD,; 高清,; 平均年龄年)被招募。所有受试者都很好地耐受 CLV-100 输注,在整个研究过程中没有不良反应,特别是在重要参数和常规血液检查中。在 6 个月时,HD 组的抗炎标志物 IL1-RA 水平显着升高(对比; )和 IL-10 (对比大号;); 和较低水平的促炎标志物 TNF (对比; )与 LD 组相比。结论。同种异体 UCMSCs CLV-100 输注在低剂量和高剂量下都是安全且耐受性良好的。大剂量输注可观察到抗炎作用。
更新日期:2020-09-28
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