Journal of Tissue Engineering and Reconstructive Surgery ›› 2024, Vol. 20 ›› Issue (4): 395-.

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Experimental study of human umbilical cord mesenchymal stem cells on recovery of cavernosum nerve function in a rat model of diabetic-induced erectile dysfunction

  

  • Online:2024-08-01 Published:2024-09-11

Abstract: Objective  To explore the restoration effects of human umbilical cord mesenchymal stem cells on erectile function in rats by repairing and regenerating cavernous nerve. Methods Umbilical cords of healthy full-term newborns were collected, human umbilical cord mesenchymal stem cells( hUCMSC) were isolated and cell surface markers were identified. The rat model of diabetes-induced erection dysfunction (DIED) was established by intra-abdominal streptozotocin (STZ) injection in combination with high-fat diet, and an apomorphine( APO) test was performed to screen diabetic rat model with erectile dysfunction after 10 weeks. Eight weeks after the transplantation of hUCMSC, erectile function was evaluated by APO test and maximum intracavernous pressure/mean arterial pressure (ICP/MAP) ratio. The levels of neuronal nitric oxide synthase (nNOS) in corpus cavernosum tissues of rats were analyzed by immunohistochemistry analysis. In addition, the expression levels of neurotrophic growth factors including BDNF, NGF, VEGF, and IGF-1 in the corpus cavernosum tissues of SD rats were detected by ELISA. Results  The hUCMSC was successfully isolated from human umbilical cords, and results of flow cytometry showed that CD73, CD90 and CD105 were highly expressed while CD11b, CD19, CD34, CD45 and HLA-DR were low expressed on the surface of P4 hUCMSC. The rat model of diabetic-induced erectile dysfunction was successfully established. After 8 weeks of hUCMSC therapy, the results of APO test showed that hUCMSC enhanced the erectile function of DIED rats, as evidenced by an increase in the number of complete erection. Compared with the negative group, the blood flow in the penis was improved as indicated by obvious increases in ICP/MAP ratio values in medium-dose and high-dose groups of hUCMSC treatment. Immunohistochemistry results suggested that after the treatment of hUCMSC in medium and high doses, hUCMSC treatment significantly elevated the expression level of nNOS in the corpus cavernosum tissue of DIED rats, then induced penile erection in rats. Furthermore, ELISA test results indicated that the expression levels of BDNF, NGF, VEGF and IGF-1 could be restored in different degrees after treatment with medium- and high-dose of hUCMSC. Conclusion hUCMSC is a kind of adult pluripotent stem cells, which is effective and dose-dependent in the treatment of DIED rats induced by high fat diet combined with STZ following intracavernosal transplantation. The mechanism of hUCMSC treatment is related to neuroprotective and regenerative repair effects provided by upregulation of the expression levels of BDNF, NGF, VEGF and IGF-1.

Key words: Human umbilical cord mesenchymal stem cells,   Diabetes mellitus,   Erectile dysfunction,   Neuronal nitric oxide synthase