{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:39:27Z","timestamp":1760060367512,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013302","name":"King Abdullah International Medical Research Center","doi-asserted-by":"publisher","award":["RC17\/202\/R"],"award-info":[{"award-number":["RC17\/202\/R"]}],"id":[{"id":"10.13039\/501100013302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (H2O2). 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\u2014major 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.<\/jats:p>","DOI":"10.3390\/ijms26168057","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:02:44Z","timestamp":1755763364000},"page":"8057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Placenta-Derived Mesenchymal Stem Cells (pMSCs) Reverse Diabetes-Associated Endothelial Complications in a Preclinical Animal Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-3179","authenticated-orcid":false,"given":"Yasser","family":"Basmaeil","sequence":"first","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-1976","authenticated-orcid":false,"given":"Ahmed","family":"Bakillah","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah Mohammed","family":"Al Subayyil","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haya Nasser","family":"Bin Kulayb","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maha Abdullah","family":"AlRodayyan","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6437-3074","authenticated-orcid":false,"given":"Abeer","family":"Al Otaibi","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sindiyan Al Shaikh","family":"Mubarak","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan S.","family":"Alamri","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, 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 11481, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-6951","authenticated-orcid":false,"given":"Altaf A.","family":"Kondkar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jahangir","family":"Iqbal","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9320-5579","authenticated-orcid":false,"given":"Tanvir","family":"Khatlani","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1161\/01.CIR.0000124725.46165.2C","article-title":"Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes","volume":"109","author":"Raitakari","year":"2004","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1747-0803.2006.00015.x","article-title":"Altered endothelial function in asymptomatic male adolescents with type 1 diabetes","volume":"1","author":"Mahmud","year":"2006","journal-title":"Congenit. 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