Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000, Cheras, Kuala Lumpur, Malaysia.
Ming Medical Sdn Bhd, D3-3 (2nd Floor), Block D3 Dana 1 Commercial Centre, Jalan PJU 1a/46, 47301, Petaling Jaya, Selangor, Malaysia.
Stem Cell Res Ther. 2024 Jun 5;15(1):160. doi: 10.1186/s13287-024-03769-2.
Metabolic syndrome (MetS) is a significant epidemiological problem worldwide. It is a pre-morbid, chronic and low-grade inflammatory disorder that precedes many chronic diseases. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) could be used to treat MetS because they express high regenerative capacity, strong immunomodulatory properties and allogeneic biocompatibility. This study aims to investigate WJ-MSCs as a therapy against MetS in a rat model.
Twenty-four animals were fed with high-fat high-fructose (HFHF) diet ad libitum. After 16 weeks, the animals were randomised into treatment groups (n = 8/group) and received a single intravenous administration of vehicle, that is, 3 × 10 cells/kg or 10 × 10 cells/kg of WJ-MSCs. A healthy animal group (n = 6) fed with a normal diet received the same vehicle as the control (CTRL). All animals were periodically assessed (every 4 weeks) for physical measurements, serum biochemistry, glucose tolerance test, cardiovascular function test and whole-body composition. Post-euthanasia, organs were weighed and processed for histopathology. Serum was collected for C-reactive protein and inflammatory cytokine assay.
The results between HFHF-treated groups and healthy or HFHF-CTRL did not achieve statistical significance (α = 0.05). The effects of WJ-MSCs were masked by the manifestation of different disease subclusters and continuous supplementation of HFHF diet. Based on secondary analysis, WJ-MSCs had major implications in improving cardiopulmonary morbidities. The lungs, liver and heart show significantly better histopathology in the WJ-MSC-treated groups than in the untreated CTRL group. The cells produced a dose-dependent effect (high dose lasted until week 8) in preventing further metabolic decay in MetS animals.
The establishment of safety and therapeutic proof-of-concept encourages further studies by improving the current therapeutic model.
代谢综合征（MetS）是全球范围内一个重要的流行病学问题。它是一种前病态的、慢性的、低度炎症性疾病，先于许多慢性疾病发生。华通氏胶来源的间充质干细胞（WJ-MSCs）可用于治疗代谢综合征，因为它们表达出高再生能力、强免疫调节特性和同种异体生物相容性。本研究旨在通过大鼠模型探讨 WJ-MSCs 作为代谢综合征治疗方法的可能性。
24 只动物自由喂食高脂肪高果糖（HFHF）饮食。16 周后，动物被随机分为治疗组（n=8/组），并接受单次静脉注射载体（即 3×10 细胞/kg 或 10×10 细胞/kg 的 WJ-MSCs）。一组 6 只健康的喂食正常饮食的动物接受与对照组（CTRL）相同的载体。所有动物定期进行体格测量、血清生化、葡萄糖耐量试验、心血管功能试验和全身成分评估。安乐死后，称重器官并进行组织病理学处理。收集血清进行 C 反应蛋白和炎症细胞因子测定。
HFHF 治疗组与健康组或 HFHF-CTRL 组之间的结果未达到统计学意义（α=0.05）。WJ-MSCs 的作用被不同疾病亚群的表现和 HFHF 饮食的持续补充所掩盖。基于二次分析，WJ-MSCs 对改善心肺并发症有重要意义。与未治疗的 CTRL 组相比，WJ-MSC 治疗组的肺、肝和心脏的组织病理学表现明显更好。细胞产生了剂量依赖性的效果（高剂量持续到第 8 周），防止代谢综合征动物的代谢进一步恶化。
安全性和治疗概念验证的确立鼓励通过改进当前的治疗模型来进行进一步的研究。
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