In vivo tracking on longer retention of transplanted myocardin gene-modified adipose-derived stem cells to improve erectile dysfunction in diabetic rats

Zhang, Hai-Bo1; Chen, Feng-Zhi2; He, Shu-Hua1; Liang, Yan-Bing3; Wang, Zhi-Qiang4; Wang, Li1; Chen, Ze-Rong1; Ding, Wei5; Zhao, Shan-Chao1; Wei, An-Yang1

2019-07-16

10.1186/s13287-019-1325-7

Stem Cell Research & Therapy   影响因子和分区

1757-6512

1757-6512

BackgroundStem cell therapy has revealed a promising future for treating erectile dysfunction (ED), but the fate and curative mechanism of intracavernosal transplanted stem cells are under further exploration. This study aimed to demonstrate the effects of myocardin gene modification on improving erectile function and prolonging the retention of implanted adipose-derived stem cells (ASCs) using in vivo small animal imaging.MethodsASCs were isolated, cultured, and identified by flow cytometry and osteogenic and adipogenic induction. The effects of gene modification on cell proliferation, apoptosis, and contraction were determined by CCK-8, EdU, flow cytometry, and collagen gel lattice contraction assays as well as confocal microscopy. A total of 20 normal and 60 diabetes mellitus ED to (DMED) Sprague-Dawley rats were recruited to the 7day and 21day groups. Each group contained subgroups of 10 rats each: the negative control (NC), DMED + ASCs plus Ad-Luc-Myocardin, DMED + ASCs plus Ad-Luc, and DMED + phosphate buffer solution (PBS) groups. Erectile function was evaluated with the intracavernosal pressure/mean arterial pressure (oICP/MAP) ratio. In vivo small animal imaging and an EdU cell tracking strategy were introduced to detect the transplanted ASCs, and IHC and WB were performed to assess smooth muscle cell protein levels.ResultsThe ASCs expressed high CD29 and CD90 and scant CD45, while the multi-induction potential was verified by oil red O and alizarin red staining. Gene transfection of myocardin had no significant influence on ASC apoptosis but inhibited cell proliferation and promoted cell contraction. Myocardin combined with ASCs enhanced the therapeutic potential of ASCs for improving the oICP/MAP ratio as well as alpha-SMA and calponin expression. In vivo imaging confirmed that ASCs resided within the cavernous body in 21days, while only a few red EdU dots were detected.ConclusionsMyocardin induced ASC differentiation towards smooth muscle-like cells and enhanced the therapeutic potential of ASCs for ameliorating ED in STZ-induced diabetic rats. Notably, in vivo small animal tracking was an effective strategy for monitoring the implanted stem cells, and this strategy might have advantages over traditional EdU assays.

Erectile dysfunction (ED) Adipose-derived stem cells (ASCs) Myocardin Cell tracking Diabetes mellitus

SCI

英语

其他

President Foundation of Nanfang Hospital, Southern Medical University[2017B001] ; President Foundation of Nanfang Hospital, Southern Medical University[2017Z014]

Cell Biology ; Research & Experimental Medicine

Cell & Tissue Engineering ; Cell Biology ; Medicine, Research & Experimental

WOS:000475880200003

BMC

Web of Science

1.Southern Med Univ, Nanfang Hosp, Dept Urol, North Guangzhou Ave 1838, Guangzhou, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2,Affiliated Hosp 1,Dept Urol, Shenzhen, Peoples R China
3.Guangzhou Med Univ, Affiliated Hosp 5, Dept Urol, Guangzhou, Guangdong, Peoples R China
4.Tungwah Hosp, Dept Urol, Dongguan, Peoples R China
5.Guiyang Univ Chinese Med, Affiliated Hosp 1, Dept Urol, Guiyang, Peoples R China

Zhang, Hai-Bo,Chen, Feng-Zhi,He, Shu-Hua,et al. In vivo tracking on longer retention of transplanted myocardin gene-modified adipose-derived stem cells to improve erectile dysfunction in diabetic rats[J]. Stem Cell Research & Therapy,2019,10.

Zhang, Hai-Bo.,Chen, Feng-Zhi.,He, Shu-Hua.,Liang, Yan-Bing.,Wang, Zhi-Qiang.,...&Wei, An-Yang.(2019).In vivo tracking on longer retention of transplanted myocardin gene-modified adipose-derived stem cells to improve erectile dysfunction in diabetic rats.Stem Cell Research & Therapy,10.

Zhang, Hai-Bo,et al."In vivo tracking on longer retention of transplanted myocardin gene-modified adipose-derived stem cells to improve erectile dysfunction in diabetic rats".Stem Cell Research & Therapy 10(2019).