PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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 × 106 cells/kg or 10 × 106 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.
RESULTS: 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.
CONCLUSIONS: The establishment of safety and therapeutic proof-of-concept encourages further studies by improving the current therapeutic model.
METHODS: 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 × 106 cells/kg or 10 × 106 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.
RESULTS: 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.
CONCLUSIONS: The establishment of safety and therapeutic proof-of-concept encourages further studies by improving the current therapeutic model.
摘要：
背景：代谢综合征（MetS）是全球范围内的重要流行病学问题。这是病前的，先于许多慢性疾病的慢性和低度炎症性疾病。Wharton的果冻来源的间充质干细胞（WJ-MSCs）可用于治疗MetS，因为它们表达高再生能力，强免疫调节特性和同种异体生物相容性。本研究旨在研究WJ-MSCs在大鼠模型中作为针对MetS的疗法。
方法:24只动物随意饲喂高脂高果糖(HFHF)饮食。16周后,将动物随机分为治疗组（n=8/组），并接受单次静脉注射载体，也就是说,3×106个细胞/kg或10×106个细胞/kg的WJ-MSC。用正常饮食喂养的健康动物组(n=6)接受与对照(CTRL)相同的载体。对所有动物进行定期评估（每4周）以进行物理测量，血清生物化学,葡萄糖耐量试验,心血管功能测试和全身成分。安乐死后,对器官进行称重和组织病理学处理。收集血清用于C-反应蛋白和炎性细胞因子测定。
结果：HFHF治疗组与健康或HFHF-CTRL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簇的表现和连续补充HFHF饮食所掩盖。根据二次分析，WJ-MSCs在改善心肺疾病方面具有重要意义。肺，与未治疗的CTRL组相比，WJ-MSC治疗组的肝脏和心脏显示出明显更好的组织病理学。细胞在防止MetS动物中的进一步代谢衰退中产生剂量依赖性效应(高剂量持续至第8周)。
结论：安全性和治疗性概念验证的建立鼓励通过改进目前的治疗模型进行进一步的研究。
方法:24只动物随意饲喂高脂高果糖(HFHF)饮食。16周后,将动物随机分为治疗组（n=8/组），并接受单次静脉注射载体，也就是说,3×106个细胞/kg或10×106个细胞/kg的WJ-MSC。用正常饮食喂养的健康动物组(n=6)接受与对照(CTRL)相同的载体。对所有动物进行定期评估（每4周）以进行物理测量，血清生物化学,葡萄糖耐量试验,心血管功能测试和全身成分。安乐死后,对器官进行称重和组织病理学处理。收集血清用于C-反应蛋白和炎性细胞因子测定。
结果：HFHF治疗组与健康或HFHF-CTRL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簇的表现和连续补充HFHF饮食所掩盖。根据二次分析，WJ-MSCs在改善心肺疾病方面具有重要意义。肺，与未治疗的CTRL组相比，WJ-MSC治疗组的肝脏和心脏显示出明显更好的组织病理学。细胞在防止MetS动物中的进一步代谢衰退中产生剂量依赖性效应(高剂量持续至第8周)。
结论：安全性和治疗性概念验证的建立鼓励通过改进目前的治疗模型进行进一步的研究。
