Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 20 2 2026 06 29 152 158 Wining Astini Program of Veterinary Paramedic, College of Vocational Studies, IPB University, Bogor, Indonesia Alif Iman Fitrianto Faculty of Veterinary Medicine, IPB University, Bogor, Indonesia Adkhilni Utami Faculty of Veterinary Medicine, IPB University, Bogor, Indonesia Adisti Dwijayanti Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia Frans Dyanagiri Suyatna Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia Adi Winarto Faculty of Veterinary Medicine, IPB University, Bogor, Indonesia Arief Boediono Faculty of Veterinary Medicine, IPB University, Bogor, Indonesia 2024 12 17 2025 12 27 Background: This study aimed to analyze the effect of repeated intravenous injections of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs), administered at a dose of 1 × 10⁶ cells/kg four times at 3-month intervals, on insulin levels and weight gain in aging female rats. Materials and Methods: Twelve female rats were divided into three groups: Group A (3-month-old young females, untreated control), Group B (24-month-old aged females injected with 0.4 mL of 0.9% NaCl as vehicle control), and Group C (24-month-old aged females injected with 1 × 10⁶ cells/kg of hWJ-MSCs suspended in 0.4 mL of 0.9% NaCl). Injections were administered at baseline and then every 3 months for a total of four doses. Twelve months after the first injection, the rats were anesthetized and sacrificed. Serum insulin levels were measured using ELISA, and immunohistochemical staining was performed to detect hWJ-MSCs homing to pancreatic tissue. Results: Rats treated with hWJ-MSCs showed a trend toward lower body weight compared to the aged vehicle-control group. Insulin levels in treated aged rats were significantly higher than those in the aged control group (p < 0.05). Immunohistochemical analysis revealed that hWJ-MSCs were extensively distributed within the islets of Langerhans of treated aged rats. Conclusion: Repeated intravenous administration of hWJ-MSCs (1 × 10⁶ cells/kg, four doses over 12 months) led to successful migration and homing to the islets of Langerhans in aging female rats. Treated animals exhibited significantly increased insulin levels and a trend toward reduced weight gain, suggesting a potential metabolic benefit of hWJ-MSC therapy in physiological aging. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/2364 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/2364/1131