Co‐overexpression of VEGF and GDNF in adipose‐derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model

Background: Recently, human multipotent adipose-derived stem cells (hMADSs) have been isolated featuring extensive expansion capacity ex vivo. However, little is known about the therapeutic efficacy of hMADS in ischemic heart diseases. We tested the hypothesis that hMADS transplantation may contribute to cardiac functional recovery following myocardial infarction (MI). Methods and Results: Nude rats were either transplanted with hMADSs (5x10 5 /rat, n=10) or PBS (control, n=9) in ischemic myocardium immediately following MI induction. The cardiac function, infarct size and capillary density in the peri-infarct area were evaluated by echocardiography and immunostaining 28 days after surgery. The cardiac function was significantly greater with increased capillary density and reduced fibrosis area in the hMADS group than that in the control group. Next, we examined tissue regeneration in the infarct heart by the transplanted hMADSs. However, remarkable differentiation of hMADSs into any cardiac cell lineages was not detected. To explore another mechanism for the favorable effect of hMADSs, we further examined mRNA expression of cytokines in hMADSs under hypoxic conditions. Although hypoxia decreased the expressions, robust VEGF, bFGF, and SDF-1α expressions were detected in hMADSs. Notably, the stem/progenitor chemokine SDF-1α expression in hMADSs was significantly greater than that in human mesenchymal stem cells that are well known to have a therapeutic effect on ischemic heart diseases. We then focused on SDF-1α /CXCR4 axis and examined the contribution of bone marrow (BM)-derived endothelial progenitor cells (EPCs), that have CXCR4 receptor for SDF-1v, to ischemic myocardium using a Tie2/LacZ BM transplantation nude mouse model. β-gal positive EPCs are frequently observed in ischemic myocardium in the hMADS group compared to the control group. Conclusion: hMADSs exhibit a therapeutic effect on cardiac function following MI with the production of VEGF, bFGF, and SDF-1α demonstrating paracrine effects rather than direct contribution to cardiac regeneration. These findings suggest that transplanted hMADSs and recruited EPCs may synergistically promote angiogenesis playing a role in ischemic myocardium.

Resveratrol enhances therapeutic effect on pancreatic regeneration in diabetes mellitus rats receiving autologous transplantation of adipose-derived stem cells

The Chinese Journal of Physiology ◽

10.4103/cjp.cjp_3_20 ◽

2020 ◽

Vol 63 (3) ◽

pp. 122

Author(s):

Chih-Yang Huang ◽

Tung-Sheng Chen ◽

Pei-Fang Lai ◽

Chia-Hua Kuo ◽

CeciliaHsuan Day ◽

...

Keyword(s):

Diabetes Mellitus ◽

Stem Cells ◽

Therapeutic Effect ◽

Autologous Transplantation ◽

Adipose Derived Stem Cells ◽

Pancreatic Regeneration

MP89-06 THERAPEUTIC EFFECTS OF ADIPOSE-DERIVED STEM CELLS-BASED MICRO-TISSUES ON ERECTILE DYSFUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

The Journal of Urology ◽

10.1016/j.juro.2016.02.2467 ◽

2016 ◽

Vol 195 (4S) ◽

Author(s):

Bicheng Yang ◽

Yu Hui ◽

Hongen Lei ◽

Ruili Guan ◽

Zhezhu Gao ◽

...

Keyword(s):

Stem Cells ◽

Erectile Dysfunction ◽

Diabetic Rats ◽

Therapeutic Effects ◽

Adipose Derived Stem Cells

Therapeutic Effect of Ligustilide-Stimulated Adipose-Derived Stem Cells in a Mouse Thromboembolic Stroke Model

Cell Transplantation ◽

10.3727/096368916x690539 ◽

2016 ◽

Vol 25 (5) ◽

pp. 899-912 ◽

Cited By ~ 6

Author(s):

Kang Chi ◽

Ru-Huei Fu ◽

Yu-Chuen Huang ◽

Shih-Yin Chen ◽

Shinn-Zong Lin ◽

...

Keyword(s):

Stem Cells ◽

Therapeutic Effect ◽

Adipose Derived Stem Cells ◽

Stroke Model ◽

Thromboembolic Stroke

Effects of Intravenous Injection of Adipose‐Derived Stem Cells in a Rat Model of Radiation Therapy‐Induced Erectile Dysfunction

Journal of Sexual Medicine ◽

10.1111/j.1743-6109.2012.02753.x ◽

2012 ◽

Vol 9 (7) ◽

pp. 1834-1841 ◽

Cited By ~ 47

Author(s):

Xuefeng Qiu ◽

Jacqueline Villalta ◽

Ludovic Ferretti ◽

Thomas M. Fandel ◽

Maarten Albersen ◽

...

Keyword(s):

Stem Cells ◽

Radiation Therapy ◽

Erectile Dysfunction ◽

Intravenous Injection ◽

Rat Model ◽

Adipose Derived Stem Cells

Implications for Differentiation of Endogenous Stem Cells: Therapeutic Effect from Icariside II on a Rat Model of Postprostatectomy Erectile Dysfunction

Stem Cells and Development ◽

10.1089/scd.2014.0380 ◽

2015 ◽

Vol 24 (6) ◽

pp. 747-755 ◽

Cited By ~ 11

Author(s):

Yongde Xu ◽

Ruili Guan ◽

Hongen Lei ◽

Zhezhu Gao ◽

Huixi Li ◽

...

Keyword(s):

Stem Cells ◽

Erectile Dysfunction ◽

Therapeutic Effect ◽

Rat Model ◽

Icariside Ii

Melatonin pretreatment can improve the therapeutic effect of Adipose-derived Stem Cells on CCl4-induced liver fibrosis

10.21203/rs.3.rs-868703/v1 ◽

2021 ◽

Author(s):

Ziqiang Zhang ◽

Yingying Sun ◽

Haojie Wang ◽

Yuxiang Yang ◽

Ruiqi Dong ◽

...

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Therapeutic Effect ◽

Control Group ◽

Group Model ◽

Adipose Derived Stem Cells ◽

Model Group ◽

Nuclear Fragmentation ◽

Apoptotic Genes ◽

And Control

Abstract Background and PurposeIn this study, the therapeutic effect of Mel-incubated ADSCs on CCl4-induced hepatic fibrosis was investigated. MethodsThe experiment was arranged into ADSCS group, ADSCS + Mel group, Model group and Control group with 10 mice in each group. The other three groups of mice were intraperitoneally injected with 8% CCl4, and the control group was injected with the same dose of PBS twice a week for 4 weeks. From the fifth week, ADSCs group and ADSCs + Mel group mice were injected with 1×106 cells/1 ml PBS dose of ADSCs and 50 μM Mel pretreated ADSCs into tail vein, respectively, twice a week for 2 weeks, and mice in the control and model groups were injected with the same dose of PBS. Samples were tested after six weeks. ResultsIn model group, severe histomathological changes were observed in liver, including severe vacuolation, nuclear fragmentation and liver fibrosis, and these changes were ameliorated by Mel pretreated ADSCs. At the same time, RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of pro-apoptotic genes (Caspase-8, Bax and Caspase-3), and promoted the expression of anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9, TGF-β, MMP-2 yellow-stained positive cells were found in the liver tissues of the model group, while the expression of positive cells was blocked by Mel-induced ADSCs. Conclusion and ImplicationsADSCs pretreated with Mel significantly improved CCl4-induced liver fibrosis, which provides a reference for clinical treatment of liver injury with mesenchymal stem cells.

Combination Therapy Using Adipose-Derived Stem Cells And Low-Intensity Extracorporeal Shockwave Therapy On Erectile Dysfunction In Streptozotocin-Induced Diabetic Rats

10.21203/rs.2.13432/v1 ◽

2019 ◽

Author(s):

Dankang Li ◽

Yongchao Ge ◽

Quanliang Hou ◽

Wenhua Wang ◽

Chengda Zhang ◽

...

Keyword(s):

Stem Cells ◽

Erectile Dysfunction ◽

Treatment Group ◽

Erectile Function ◽

Combined Treatment ◽

Adipose Derived Stem Cells ◽

Model Group ◽

Extracorporeal Shockwave Therapy ◽

Shockwave Therapy ◽

Low Intensity

Abstract Background：Diabetes mellitus (DM) is an important risk factor for erectile dysfunction (ED). Adipose-derived stem cells (ADSCs) and low-intensity extracorporeal shockwave therapy (LI-ESWT) are two emerging therapies for ED. The efficacy of ADSCs combined LI-ESWT in the treatment of diabetes induced erectile dysfunction (DMED) was not completely elucidated. This study aim to investigate combined therapeutic efficacy of ADSCs and LI-ESWT in rat model of DMEDand whether they have interaction.Methods：Rats were randomly divided into 5 groups: control, erectile dysfunction group (ED), ADSCs treatment group(ADSCs), LI-ESWT treatment group (LI-ESWT) and ADSCs combined with LI-ESWT treatment (ADSCs+LI-ESWT). After 4 weeks, erectile function was assessed using intracavernous pressure (ICP) and mean arterial pressure (MAP), after that performed immunohistochemistry (IH).Results：Finally, a total of 98 rats completed the experiment. The ICP/MAP of five groups under the voltage stimulation of 10V was significantly different (P>0.05). ICP/MAP in ADSC group, LI-ESWT group and combined treatment group was significantly higher than that of ED model group; ICP/MAP in combined treatment group was higher than ADSC group and LI-ESWT group. Interaction between LI-ESWT and ADSCs therapy was not statistically significant (P＞0.05).The expression of -smooth muscle actin (-SMA), nerve nitricoxide synthase (nNOS) and von Willebrand factor (vWF) in ADSCs treatment group, LI-ESWT group and combined treatment group was higher than those in ED model group (P < 0.05).Conclusions：Both ADSCs and LI-ESWT therapy can improve the erectile function of rats. The combination of these two methods present better effect on ED than used individually. There is no positive interaction between ADSCs therapy and LI-ESWT. Both ADSCs and LI-ESWT can enhance the expression of α-SMA, nNOS and vWF in corpus cavernosum of ED rats.

Transplantation of adipose derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus induced erectile dysfunction in rats

10.7287/peerj.preprints.27737v1 ◽

2019 ◽

Author(s):

Yan Zhang ◽

Jun Yang ◽

Li Zhuan ◽

Guanghui Zang ◽

Tao Wang ◽

...

Keyword(s):

Nitric Oxide ◽

Diabetes Mellitus ◽

Stem Cells ◽

Smooth Muscle ◽

Erectile Dysfunction ◽

Inducible Nitric Oxide Synthase ◽

Collagen Iv ◽

Adipose Derived Stem Cells ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Background: Erectile dysfunction is a major complication of diabetes mellitus. Adipose derived stem cells (ADSCs) has attracted much attention as a promising tool for the treatment of diabetes mellitus induced erectile dysfunction (DMED). Inducible nitric oxide synthase (iNOS) plays an important role in protecting penile tissues from fibrosis. The aim of this study was to determine the efficacy of ADSCs overexpressing iNOS on DMED in rats. Methods: ADSCs were isolated and infected with adenovirus overexpressing iNOS (named as ADSCs-iNOS). The expression of iNOS was detected using western blot analysis and real-time PCR. Rats were randomly assigned into five groups: control group, DMED group, ADSCs group, ADSCs-EGFP group and ADSCs-iNOS group. 5×105 cells were given once via the intracorporal route. Two weeks after treatment, erectile function was assessed by electrical stimulation of the cavernous nerve. Penile tissues were obtained and evaluated at histology level. Results: We found that ADSCs-iNOS had significantly higher expression of iNOS at mRNA and protein levels and generated more nitric oxide. ADSCs-iNOS reduced collagen I and collagen IV expression of corpus cavernosum smooth muscle cells (CCSMCs) in cell co-culture model. Transforming growth factor-β1 expression and p-Smad2/3 to Smad2/3 ratio in CCSMCs reduced following co-culture with ADSCs-iNOS. Injection of ADSCs-iNOS significantly ameliorated DMED in rats and decreased collagen/smooth muscle cell ratio of penile tissues. Moreover, elevated nitric oxide and cGMP concentrations were detected in penile tissues of ADSCs-iNOS group. Conclusion: Taken together, ADSCs-iNOS significantly improve erectile function of DMED rats. The therapeutic effect may be achieved by increased nitric oxide generation and the suppression of collagen I and collagen IV expression in the CCSMCs to decrease penile fibrosis.