Basmaeil Yasser, Bakillah Ahmed, Al Subayyil Abdullah Mohammed, Bin Kulayb Haya Nasser, AlRodayyan Maha Abdullah, Al Otaibi Abeer, Mubarak Sindiyan Al Shaikh, Alamri Hassan S, Kondkar Altaf A, Iqbal Jahangir, Khatlani Tanvir
Stem Cell Research Unit, Blood and Cancer Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11426, Saudi Arabia.
Biomedical Research Core, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al Ahsa 31982, Saudi Arabia.
Int J Mol Sci. 2025 Aug 20;26(16):8057. doi: 10.3390/ijms26168057.
Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide (HO). This oxidative stress impairs endothelial cells, which are vital for vascular health, leading to severe complications such as diabetic nephropathy, retinopathy, and coronary artery disease-major causes of morbidity and mortality in diabetic patients. Recent studies have highlighted the therapeutic potential of placenta-derived mesenchymal stem cells (pMSCs), in mitigating these complications. pMSCs exhibit anti-inflammatory, antioxidant, and tissue-repair properties, showing promise in reversing endothelial damage in laboratory settings. To explore their efficacy in a more physiologically relevant context, we used a streptozotocin (STZ)-induced diabetic mouse model, which mimics type 1 diabetes by destroying pancreatic beta cells and causing hyperglycemia. pMSCs were administered via intra-peritoneal injections, and their effects on endothelial injury and tissue damage were assessed. Metabolic tests, including glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) revealed that pMSCs did not restore metabolic homeostasis or improve glucose regulation. However, histopathological kidney, heart, and eye tissue analyses demonstrated significant protective effects. pMSCs preserved glomerular structure in the kidneys, protected cardiac blood vessels, and maintained retinal integrity, suggesting their potential to address diabetes-related tissue injuries. Although these findings underscore the therapeutic potential of pMSCs for diabetic complications, further research is needed to optimize dosing, elucidate molecular mechanisms, and evaluate long-term safety and efficacy. Combining pMSCs with other therapies may enhance their benefits, paving the way for future clinical applications.
糖尿病越来越被认为是一种以全身代谢紊乱为特征的慢性炎症性疾病，内皮功能障碍在其并发症中起着核心作用。高血糖是糖尿病的一个标志，它通过诱导过量的活性氧（ROS）产生，特别是过氧化氢（HO），导致内皮损伤。这种氧化应激损害了对血管健康至关重要的内皮细胞，从而导致严重的并发症，如糖尿病肾病、视网膜病变和冠状动脉疾病，这些是糖尿病患者发病和死亡的主要原因。最近的研究强调了胎盘来源的间充质干细胞（pMSCs）在减轻这些并发症方面的治疗潜力。pMSCs具有抗炎、抗氧化和组织修复特性，在实验室环境中显示出逆转内皮损伤的前景。为了在更符合生理的背景下探索它们的疗效，我们使用了链脲佐菌素（STZ）诱导的糖尿病小鼠模型，该模型通过破坏胰腺β细胞并导致高血糖来模拟1型糖尿病。通过腹腔注射给予pMSCs，并评估它们对内皮损伤和组织损伤的影响。包括葡萄糖耐量试验（GTTs）和胰岛素耐量试验（ITTs）在内的代谢测试表明，pMSCs不能恢复代谢稳态或改善血糖调节。然而，肾脏、心脏和眼睛组织的组织病理学分析显示出显著的保护作用。pMSCs保留了肾脏中的肾小球结构，保护了心脏血管，并维持了视网膜的完整性，表明它们有潜力解决与糖尿病相关的组织损伤。尽管这些发现强调了pMSCs对糖尿病并发症的治疗潜力，但仍需要进一步研究来优化给药剂量、阐明分子机制，并评估长期安全性和疗效。将pMSCs与其他疗法相结合可能会增强它们的益处，为未来的临床应用铺平道路。
