Safety Evaluation and Biodistribution of Fetal Umbilical Cord Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Sprague Dawley Rats
Year: 2025
Type: article
Abstract: Umbilical cord mesenchymal stem cells (UCMSCs)-derived small extracellular vehicles (sEVs) are reported to offer therapeutic effects in regenerative medicine, but they lack safety and biodistribution profiles to support smooth translation at the clinical stage and regulatory requirements. Our study aimed to determine the safety and biodistribution profile in a healthy animal model before application in the metabolic syndrome model. Method: Healthy male Sprague Dawley (SD) rats were given an intravenous (IV) injection of normal saline (control group) or pooled fetal UCMSCs-derived sEVs (treated group) every three weeks for 90 days. Morbidity and mortality observation (daily), physical measurements (weekly), selected serum biochemistry (every three weeks), and hematology (every three weeks) were performed for 90 days. Acute toxicity (on day 14) and sub-chronic toxicity (on day 90) were assessed for gross necropsy, relative organ weight, and histopathological assessment of lungs, liver, spleen, kidney, and lymph nodes. Separately, a biodistribution study was conducted with the sEVs preparations labeled with PKH26 fluorescent dye, given intravenously to the rats. The organs were harvested 24 h post-injection. There were no drastic changes in either group's morbidity or mortality, physical, hematological, and biochemistry evaluation. The histopathological assessment concluded moderate (focal) inflammation in the treated group's kidneys and signs of recovery from the inflammation and vascular congestion in the liver. A biodistribution study revealed a higher accumulation of sEVs in the spleen. Multiple IV injections of the pooled fetal UCMSCs-derived sEVs in healthy male SD rats were deemed safe. The sEVs were abundantly distributed in the spleen 24 h post-injection.
DOI: 10.3390/ijms26146806
Authors: Illayaraja Krishnan, Ubashini Vijakumaran, Ng Min Hwei, Law Jia Xian, Mohd Rafizul Mohd Yusof, Thavachelvi Thangarajah, Tan Geok Chin, Yin Ping Wong, Anusha Kalyanasundaram, Zalina Mahmood, Shathiya Rajamanickam, Baskar Subramani, Yogeswaran Lokanathan
Institution: National University of Malaysia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funder: Universiti Kebangsaan Malaysia
OpenAlex ID: W4412472663