MP38-08: human umbilical cord mesenchymal stem cells ameliorate erectile dysfunction in type I and type II diabetes mellitus rats through the attenuation of ferroptosis by SLC7A11/GPX4/ACSL4 pathway

Huan Feng*, Tao Wang, Jihong Liu, Wuhan, China, People's Republic of

Introduction: Diabetic Erectile Dysfunction (DMED) is a common complication of diabetes, which seriously impairs the life of male patients of all ages. Diabetes could destroy various cells in the corpus cavernosum, such as nerve cells, endothelial cells, smooth muscle cells. Human Umbilical Cord Mesenchymal Stem Cells (hUCMSCs) are cells with multipotential differentiation potential.The present study aims to investigate the therapeutic role and mechanism of hUCMSCs on type I and type II diabetes mellitus rats.

Methods: Fifty male Sprague-Dawley rats received intraperitoneal injection with streptozotocin for 3 days to induce type 1 diabetes. Another 50 male ZDF rats were fed with Purina 5008 to induce type 2 DMED. After 8 weeks, type 1 and type 2 DMED rats were separately selected by the apomorphine (APO) test. Both of types DMED rats were divided into normal control group (NC), diabetic group (DM), cavernous injection (1×106 ) group (CI), tail vein injection (1×106 ) group (VI). Stem cells were labeled with Edu prior to injection for subsequent observation. Primary corpus cavernous smooth muscle cells(CCSMCs) from healthy rats were cultured and treated with berberine. Mitochondria in ccSMCs were observed by transmission electron microscopy (TEM).

Results: None of rats received stem cell injection had obvious adverse reactions. Injection of hUCMSCs improved erectile function, reduced levels of NADPH oxidases, ROS production and tissue iron content. Among the type 1 DMED rats, the results showed that mICP/MAP of DM (0.232±0.082 mmHg) was significantly lower than NC (0.793±0.153 mmHg), CI (0.333±0.104 mmHg) and VI (0.384±0.095 mmHg) were improved compared with DM, and similar phenomenon also showed among the type 2 DMED rats. Besides, co-cultured CCSMCs with hUCMSCs exhibited a lower level of ferroptosis by SLC7A11/GPX4/ACSL4 pathway with high glucose (HG) treatment. TEM showed that the mitochondria shrunk, the cristae of mitochondria were destroyed, and exhibited high electron density in CCSMCs treated with HG, and these effects could be obviously reversed by hUCMSCs.

Conclusions: human umbilical cord mesenchymal stem cells can safely and effectively ameliorate erectile dysfunction in both type I and type II diabetes mellitus rats, and attenuate ferroptosis of CCSMCs through SLC7A11/GPX4/ACSL4 pathway. It provides preclinical evidence for application of hUCMSCs to DMED treatment and potential molecular mechanism of it.

Source of Funding: None