Mesenchymal Stem Cells Enhance Vascular Endothelial Growth Factor-A, Endothelial Nitric Oxide Synthetase, and HSP70 Expression in Improving Erectile Dysfunction in Streptozotocin-induced Diabetic Rats

Ade Indra Mukti; Syafruddin Ilyas; Syah Mirsya Warli; Agung Putra; Nur Rasyid; Delfitri Munir; Kamal Basri Siregar; Muhammad Ichwan; Iffan Alif; Nurul Hidayah

doi:10.3889/oamjms.2021.7801

Authors

Ade Indra Mukti Department of Doctoral Degree Program, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
Syafruddin Ilyas Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia
Syah Mirsya Warli Department of Urology, Faculty of Medicine, Universitas Sumatera Utara Hospital, Medan, Indonesia
Agung Putra Stem Cell and Cancer Research, Faculty of Medical, Sultan Agung Islamic University, Semarang, Indonesia; Department of Pathology, Medical Faculty, Sultan Agung Islamic University, Semarang, Indonesia; Department of Postgraduate Biomedical Science, Medical Faculty, Sultan Agung Islamic University, Semarang, Indonesia https://orcid.org/0000-0003-4261-9437
Nur Rasyid Department of Urology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
Delfitri Munir Department of Doctoral Degree Program, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; Pusat Unggulan IPTEK Tissue Engineering, Universitas Sumatera Utara, Medan, Indonesia
Kamal Basri Siregar Department of Oncology Surgery, Faculty of Medicine, Universitas Sumatera Utara, Universitas Sumatera Utara Hospital, Medan, Indonesia
Muhammad Ichwan Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia https://orcid.org/0000-0001-8380-9099
Iffan Alif Stem Cell and Cancer Research, Faculty of Medical, Sultan Agung Islamic University, Semarang, Indonesia
Nurul Hidayah Stem Cell and Cancer Research, Faculty of Medical, Sultan Agung Islamic University, Semarang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7801

Keywords:

Mesenchymal stem cells, Erectile dysfunction, Vascular endothelial growth factor A-A, Endothelial nitric oxide synthetase, HSP70

Abstract

This study investigated the therapeutic role of mesenchymal stem cells (MSCs) on erectile function in a diabetes mellitus erectile dysfunction (DMED) rat model by analyzing the expression of endothelial nitric oxide synthetase (eNOS), vascular endothelial growth factor (VEGF), and the 70 kilodalton heat shock proteins (HSP70). MSCs were isolated from umbilical cords (UCs), and their characteristics identified by flow cytometry and osteogenic differentiation analysis. Thirty 8-week-old rats were divided into four groups: sham, control, T1, and T2. After a 16 h fast, 24 rats were randomly selected and intraperitoneally injected with streptozotocin (STZ) to induce DM. At 8 weeks after STZ injection, rats with DMED were classified into four groups, sham, control group [DMED rats received 500 μL phosphate buffer saline (PBS)]; T1 [DMED rats treated with 500 μL PBS containing 1 × 10⁶ UC-MSCs]; T2 [DMED rats treated with 500 μL PBS containing 2 × 10⁶ UC-MSCs]. Eight weeks after MSCs administration, the rats’ erectile function was measured by cavernous nerve stimulation. The blinded histological and gene expression assessment were used to analyze the eNOS, HSP70 content, and VEGF expression on the penile tissues. MSCs administration, rats in T1 and T2 groups showed a significant enhancement of erectile response that showed a trend of increase of VEGF mRNA level expression was 2.2 ± 0.61 in T2 Group supported with the optimum recovery of eNOS, in which the value of eNOS expression was 20.66% ± 2.32%. While optimum decrease of HSP70 content, the value of HSP70 expression was 15.50% ± 0.90%. IHC results showed that the DMED induction in rats caused a significant decrease of eNOS content in corpus cavernosum tissue. MSCs could ameliorate DMED in rats by increasing VEGF and decreasing HSP70 and eNOS, indicating these cells offer a potential application for DMED patients’ treatment.

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