Chin Sze-Piaw, Mohd-Shahrizal Mohd-Yusoff, Liyana Mohd-Zuhar, Then Kong Yong, Cheong Soon Keng
NSCMH Medical Centre, Seremban, Negeri Sembilan, Malaysia.
Cytopeutics, Cyberjaya, Malaysia.
Stem Cells Int. 2020 Sep 28;2020:8877003. doi: 10.1155/2020/8877003. eCollection 2020.
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. . 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-).
11 healthy subjects (LD, = 5; HD, = 6; mean age of 55 ± 13 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 (705 ± 160 vs. 306 ± 36 pg/mL; = 0.02) and IL-10 (321 ± 27 vs. 251 ± 28 pg/mL; = 0.02); and lower levels of proinflammatory marker TNF- (74 ± 23 vs. 115 ± 15 pg/mL; = 0.04) compared to LD group.
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.
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及其他细胞因子。MSCs还具有免疫豁免权，排斥风险低。脐带间充质干细胞（UCMSCs）作为紧急医疗状况下现成的同种异体治疗方法，特别具有吸引力。我们旨在确定马来西亚雪兰莪Cytopeutics公司生产的UCMSCs（CLV - 100）静脉内同种异体输注在健康志愿者中的安全性和有效性，并确定观察到免疫调节作用的有效剂量。在获得父母双方书面同意后，于足月健康婴儿出生后采集脐带样本。对三代人（新生儿、父母和祖父母）进行基因突变、感染、癌症及其他遗传性疾病筛查。样本被转移至经认证的药品生产质量管理规范实验室进行处理。受试者接受低剂量（LD，6500万个细胞）或高剂量（HD，1.3亿个细胞）的CLV - 100输注，并随访6个月。我们使用酶联免疫吸附测定法（ELISA）检测细胞因子，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）、促炎/抗炎细胞因子白细胞介素6（IL - 6）以及促炎细胞因子肿瘤坏死因子 - α（TNF - ）。
招募了11名健康受试者（LD组5名；HD组6名；平均年龄55±13岁）。在整个研究过程中，所有受试者对CLV - 100输注耐受性良好，未出现不良反应，尤其是生命体征参数和常规血液检查方面。6个月时，HD组抗炎标志物IL1 - RA（705±160 vs. 306±36 pg/mL；P = 0.02）和IL - 10（321±27 vs. 251±28 pg/mL；P = 0.02）水平显著更高；与LD组相比，促炎标志物TNF - （74±23 vs. 115±15 pg/mL；P = 0.04）水平更低。
同种异体UCMSCs CLV - 100低剂量和高剂量输注均安全且耐受性良好。高剂量输注可观察到抗炎作用。
