Bhirau Wilaksono, Agung Putra, Chodidjah, Mas Rizky A. A. Syamsunarno, Prasetyowati Subchan, Titiek Sumarawati, Nurul Hidayah, Mohammad Ariq Nazar
Diabetes accelerates neurodegeneration, partly through CD38-mediated NAD+depletion and cellular senescence. Secretome hypoxia mesenchymal stem cells (S-HMSCs) secrete anti-inflammatory factors such as IL-10, which may counteract neurodegenerative damage. This study evaluated the effects of S-HMSC therapy on CD38, p16, p21, and SIRT1 expression in the brains of STZ-induced diabetic rats. Male Wistar rats were divided into four groups: SHAM (healthy control), C (diabetic control), P1 (500 µL S-HMSC), and P2 (1000 µL S-HMSC). Diabetes was induced using streptozotocin (65 mg/kg, IP), confirmed by blood glucose >200 mg/dL. S-HMSCs were administered intraperitoneally on days 0, 7, 14, and 21. CD38 expression was assessed using immunohistochemistry (IHC); p16, p21, and SIRT1 were analyzed by qRT-PCR. CD38 expression significantly decreased in P1 (12.72 ± 2.65) and P2 (8.43 ± 1.01) compared to C (19.07 ± 2.70). p16 and p21 expression levels were significantly reduced in P1 and P2 compared to C (P < 0.05). SIRT1 was significantly upregulated in P1 (2.48) but downregulated in P2 (0.67), suggesting a nonlinear dose response. S-HMSC therapy reduces CD38 expression and senescence markers (p16, p21) in the diabetic brain. However, SIRT1 expression exhibits a biphasic dose response. These findings support the potential of S-HMSC therapy for modulating neurodegeneration in diabetes. © 2026, University of Malaya. All rights reserved.
Faculty of Medicine, Sultan Agung Islamic University (UNISSULA), Central Java, Semarang, Indonesia; Stem Cell and Cancer Research (SCCR) Laboratory, Central Java, Semarang, Indonesia; Department of Postgraduate Biomedical Science, Faculty of Medicine, Sultan Agung Islamic University (UNISSULA), Central Java, Semarang, Indonesia; Department of Pathological Anatomy, Faculty of Medicine, Sultan Agung Islamic University (UNISSULA), Central Java, Semarang, Indonesia; Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, West Java, Bandung, Indonesia; Department of Dermatology and Venereology, Faculty of Medicine, Diponegoro University, Central Java, Semarang, Indonesia; Department of Biochemistry, Faculty of Medicine, Universitas Negeri Makassar, South Sulawesi, Makassar, Indonesia; Center of Excellence for Healthy Longevity and Physical Fitness, Faculty of Medicine, Universitas Negeri Makassar, Indonesia; Department of Biotechnology, Institute Karya Mulia Bangsa, Central Java, Semarang, Indonesia; Department of Biomedical Science, Institute Karya Mulia Bangsa, Central Java, Semarang, Indonesia
