PMID- 36064453 OWN - NLM STAT- MEDLINE DCOM- 20220908 LR - 20220922 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 13 IP - 1 DP - 2022 Sep 5 TI - Human umbilical cord mesenchymal stem cells ameliorate erectile dysfunction in rats with diabetes mellitus through the attenuation of ferroptosis. PG - 450 LID - 10.1186/s13287-022-03147-w [doi] LID - 450 AB - BACKGROUND: Erectile dysfunction (ED), as one of the most prevalent consequences in male diabetic patients, has a serious impact on men's physical and mental health, and the treatment effect of diabetic mellitus erectile dysfunction (DMED) is often worse. Therefore, the development of a novel therapeutic approach is urgent. As stem cells with high differentiation potential, human umbilical cord mesenchymal stem cells (HUCMSCs) have been widely used in the treatment of diseases in other systems, and are expected to be a promising strategy for the treatment of DMED. In this study, we investigated the role of HUCMSCs in managing erectile function in rat models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and compared the effects of two different injection methods. METHODS: T1DM and T2DM ED rats were given labelled HUCMSCs by corpus cavernosum injection and tail vein injection, respectively. ICP and MAP were monitored simultaneously by electrical stimulation four weeks after injection to indicate the erectile function of rats. To track the development and colonisation capabilities of stem cells, we performed EdU assay with penile tissue. The histological changes of the penis were observed by hematoxylin-eosin staining, and Masson's trichrome staining was conducted to evaluate the smooth muscle content and the degree of fibrosis in the rat penis. Then, we employed specific kits to measure the level of NO, cGMP, MDA, SOD and Fe in penis. Electron transmission microscopy was implemented to observe morphology of mitochondria. Besides, western blot and immunofluorescence staining were performed to demonstrate the expression of ferroptosis-related genes. RESULTS: We found that HUCMSCs improved erectile function in T1DM and T2DM ED rats, with no difference in efficacy between corpus cavernosum injection and tail vein injection. The EdU assay revealed that only a tiny percentage of HUCMSCs colonised the corpus cavernosum, while smooth muscle in the penis expanded and collagen decreased following HUCMSC injection. Moreover, the levels of oxidative stress in the penis of the rats given HUCMSCs were dramatically reduced, as was the tissue iron content. HUCMSCs normalised mitochondrial morphology within corpus cavernosum smooth muscle cells (CCSMCs), which were characteristically altered by high glucose. Furthermore, the expression of ferroptosis inhibitory genes SLC7A11 and GPX4 was obviously elevated in CCSMCs after stem cell management, but the abundances of ACSL4, LPCAT3 and ALOX15 showed the polar opposite tendency. CONCLUSIONS: HUCMSCs can effectively and safely alleviate erectile dysfunction in T1DM and T2DM ED rats, while restoring erectile function by attenuating diabetes-induced ferroptosis in CCSMCs. Additionally, this study provides significant evidence for the development of HUCMSCs as a viable therapeutic strategy for DMED. CI - (c) 2022. The Author(s). FAU - Feng, Huan AU - Feng H AD - Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Liu, Qi AU - Liu Q AD - Department of Urology, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, China. FAU - Deng, Zhiyao AU - Deng Z AD - Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, Guangdong, China. FAU - Li, Hao AU - Li H AD - Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Zhang, Huajie AU - Zhang H AD - Department of Urology, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, China. FAU - Song, Jingyu AU - Song J AD - Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Liu, Xiaming AU - Liu X AD - Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Liu, Jihong AU - Liu J AD - Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Wen, Bo AU - Wen B AD - Department of Urology, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, China. tjwb001@126.com. FAU - Wang, Tao AU - Wang T AUID- ORCID: 0000-0003-2952-8397 AD - Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. twang@tjh.tjmu.edu.cn. AD - Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, Guangdong, China. twang@tjh.tjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220905 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 SB - IM MH - Animals MH - *Diabetes Mellitus, Type 1 MH - *Diabetes Mellitus, Type 2 MH - *Erectile Dysfunction/therapy MH - *Ferroptosis MH - Humans MH - Male MH - *Mesenchymal Stem Cells/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Umbilical Cord/metabolism PMC - PMC9444126 OTO - NOTNLM OT - Erectile dysfunction OT - Ferroptosis OT - Human umbilical cord mesenchymal stem cells OT - Type 1 diabetes mellitus OT - Type 2 diabetes mellitus COIS- The authors have declared that no competing interest exists. EDAT- 2022/09/06 06:00 MHDA- 2022/09/09 06:00 PMCR- 2022/09/05 CRDT- 2022/09/05 23:40 PHST- 2022/03/30 00:00 [received] PHST- 2022/08/18 00:00 [accepted] PHST- 2022/09/05 23:40 [entrez] PHST- 2022/09/06 06:00 [pubmed] PHST- 2022/09/09 06:00 [medline] PHST- 2022/09/05 00:00 [pmc-release] AID - 10.1186/s13287-022-03147-w [pii] AID - 3147 [pii] AID - 10.1186/s13287-022-03147-w [doi] PST - epublish SO - Stem Cell Res Ther. 2022 Sep 5;13(1):450. doi: 10.1186/s13287-022-03147-w.