Motawea Shaimaa M, Noreldin Rasha I, Naguib Yahya M
1Clinical Physiology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
2Clinical Pathology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
Diabetol Metab Syndr. 2020 May 11;12:40. doi: 10.1186/s13098-020-00546-y. eCollection 2020.
Diabetes mellitus in elderly represents an exceptional subset in the population vulnerable to cardiovascular events. As aging, diabetes mellitus and hypertension share common pathways, an ideal treatment should possess the ability to counter more than one of, if not all, the underlying mechanisms. Stem cells emerged as a potential approach for complicated medical problems. We tested here the possible role of trans-differentiated endothelial cells (ECs) in the treatment of diabetes mellitus in old rats.
Mesenchymal stem cells where isolated from umbilical cord Wharton's Jelly and induced to differentiate into endothelial like-cells using vascular endothelial growth factor-enriched media. Thirty aged male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control group (18-20 months old, weighing 350-400 g, received single intraperitoneal injection as well as single intravenous injection via tail vein of the vehicles), aged diabetic group (18-20 months old, weighing 350-400 g, received single intraperitoneal injection of 50 mg/kg streptozotocin, and also received single intravenous injection of saline via tail vein), and aged diabetic + ECs group (18-20 months old, weighing 350-400 g, received single intraperitoneal injection of 50 mg/kg streptozotocin, and also received single intravenous injection of 2*10 MSC-derived ECs in 0.5 ml saline via tail vein) groups. Assessment of SBP, aortic PWV, and renal artery resistance was performed. Serum levels of ET1, ANG II, IL-6, TNF-α, MDA, ROS, and VEGF were evaluated, as well as the aortic NO tissue level and eNOS gene expression. Histopathological and immunostaining assessments of small and large vessels were also performed.
Induction of diabetes in old rats resulted in significant increase in SBP, aortic PWV, renal artery resistance, and serum levels of ET1, ANG II, IL-6, TNF-α, MDA, ROS, and VEGF. While there was significant decrease in aortic NO tissue level and eNOS gene expression in the aged diabetic group when compared to aged control group. ECs treatment resulted in significant improvement of endothelial dysfunction, inflammation and oxidative stress.
We report here the potential therapeutic role of trans-differentiated ECs in aged diabetics. ECs demonstrated anti-inflammatory, antioxidant, gene modifying properties, significantly countered endothelial dysfunction, and improved vascular insult.
老年糖尿病是易发生心血管事件人群中的一个特殊亚组。随着年龄增长，糖尿病和高血压有共同的发病机制，理想的治疗方法应具备应对一种以上（甚至全部）潜在机制的能力。干细胞已成为解决复杂医学问题的一种潜在方法。我们在此测试了转分化内皮细胞（ECs）在老年大鼠糖尿病治疗中的可能作用。
从脐带华通氏胶中分离间充质干细胞，并用富含血管内皮生长因子的培养基诱导其分化为内皮样细胞。本研究使用了30只老年雄性Wistar白化大鼠。大鼠被分为（每组10只）：对照组（18 - 20个月大，体重350 - 400克，接受单次腹腔注射以及通过尾静脉单次静脉注射赋形剂）、老年糖尿病组（18 - 20个月大，体重350 - 400克，接受单次腹腔注射50毫克/千克链脲佐菌素，也通过尾静脉接受单次静脉注射生理盐水）和老年糖尿病 + ECs组（18 - 20个月大，体重350 - 400克，接受单次腹腔注射50毫克/千克链脲佐菌素，也通过尾静脉接受单次静脉注射0.5毫升生理盐水中的2×10个间充质干细胞来源的内皮细胞）。进行收缩压、主动脉脉搏波速度（PWV）和肾动脉阻力的评估。评估血清中内皮素 - 1（ET1）、血管紧张素II（ANG II）、白细胞介素 - 6（IL - 6）、肿瘤坏死因子 - α（TNF - α）、丙二醛（MDA）及活性氧（ROS）、血管内皮生长因子（VEGF）的水平，以及主动脉一氧化氮（NO）组织水平和内皮型一氧化氮合酶（eNOS）基因表达。还对小血管和大血管进行组织病理学和免疫染色评估。
老年大鼠诱导糖尿病后，收缩压、主动脉脉搏波速度、肾动脉阻力以及血清中ET1、ANG II、IL - 6、TNF - α、MDA、ROS和VEGF水平显著升高。与老年对照组相比，老年糖尿病组主动脉NO组织水平和eNOS基因表达显著降低。内皮细胞治疗导致内皮功能障碍、炎症和氧化应激得到显著改善。
我们在此报告了转分化内皮细胞在老年糖尿病患者中的潜在治疗作用。内皮细胞表现出抗炎、抗氧化、基因修饰特性，显著对抗内皮功能障碍，并改善血管损伤。
