scholarly journals Embryonic stem cell-derived extracellular vesicle-mimetic nanovesicles rescue erectile function by enhancing penile neurovascular regeneration in the streptozotocin-induced diabetic mouse

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mi-Hye Kwon ◽  
Kang-Moon Song ◽  
Anita Limanjaya ◽  
Min-Ji Choi ◽  
Kalyan Ghatak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Embryonic Stem Cell ◽  
Clinical Application ◽  
High Glucose ◽  
Erectile Function ◽  
Embryonic Stem ◽  
Neural Regeneration ◽  
High Glucose Condition ◽  
Glucose Condition

AbstractExtracellular vesicles (EVs) have attracted particular interest in various fields of biology and medicine. However, one of the major hurdles in the clinical application of EV-based therapy is their low production yield. We recently developed cell-derived EV-mimetic nanovesicles (NVs) by extruding cells serially through filters with diminishing pore sizes (10, 5, and 1 μm). Here, we demonstrate in diabetic mice that embryonic stem cell (ESC)-derived EV-mimetic NVs (ESC-NVs) completely restore erectile function (~96% of control values) through enhanced penile angiogenesis and neural regeneration in vivo, whereas ESC partially restores erectile function (~77% of control values). ESC-NVs promoted tube formation in primary cultured mouse cavernous endothelial cells and pericytes under high-glucose condition in vitro; and accelerated microvascular and neurite sprouting from aortic ring and major pelvic ganglion under high-glucose condition ex vivo, respectively. ESC-NVs enhanced the expression of angiogenic and neurotrophic factors (hepatocyte growth factor, angiopoietin-1, nerve growth factor, and neurotrophin-3), and activated cell survival and proliferative factors (Akt and ERK). Therefore, it will be a better strategy to use ESC-NVs than ESCs in patients with erectile dysfunction refractory to pharmacotherapy, although it remains to be solved for future clinical application of ESC.

scholarly journals PD49-03 EFFECT OF INTRACAVERNOUS ADMINISTRATION OF EMBRYONIC STEM CELL-DERIVED EXOSOME ON ERECTILE FUNCTION IN THE STREPTOZOTOCIN-INDUCED DIABETIC MOUSE

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Mi-hye Kwon ◽  
Kang-Moon Song ◽  
Kalyan Ghatak ◽  
Nhat Minh Nguyen ◽  
Min-Ji Choi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Erectile Function ◽  
Embryonic Stem ◽  
Diabetic Mouse

Neural conversion of human embryonic stem cell colonies in the presence of fibroblast growth factor-2

Neuroreport ◽  
2006 ◽  
Vol 17 (16) ◽  
pp. 1675-1681 ◽  
Author(s):  
Corinne Benzing ◽  
Michaela Segschneider ◽  
Anke Leinhaas ◽  
Joseph Itskovitz-Eldor ◽  
Oliver Br??stle
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Embryonic Stem Cell ◽  
Fibroblast Growth Factor ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth

HP-01-006 Embryonic stem cell-derived exosome rescues erectile function by penile angiogenesis and neurovascular regeneration in the biabetic mouse

2019 ◽  
Vol 16 (5) ◽  
pp. S32
Author(s):  
N.-M. Nguyen ◽  
M.-H. Kwon ◽  
K.-M. Song ◽  
A. Limanjaya ◽  
M.-J. Choi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Erectile Function ◽  
Embryonic Stem

206 ESTIMATION OF EMBRYO DEVELOPMENTAL TOXICANTS IN HUMAN EMBRYONIC STEM CELL

2014 ◽  
Vol 26 (1) ◽  
pp. 217
Author(s):  
E. M. Jung ◽  
Y. Choi ◽  
H. S. Kang ◽  
E. K. Shin ◽  
E. B. Jeung
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Growth Factor ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Dependent Manner ◽  
Es Cell ◽  
Cell Markers ◽  
The Mean ◽  
Hes Cells

An embryonic stem cell test (EST) has been developed to evaluate the embryotoxic potential of chemicals with an in vitro system. In the present study, novel methods to screen toxic chemicals during the developmental process were evaluated using undifferentiated human embryonic stem (hES: H9) cells. hES H9 cells were obtained from WiCell Research Institute, Inc., (Madison, WI, USA) and cultured according to the manufacturer's protocol. The cells were cultured on mouse embryonic fibroblast (mEF) cells in hES cell medium composed of DMEM/F12 supplemented with 20% defined fetal bovine serum (FBS), 1% minimal essential medium (MEM) nonessential amino acids, 0.1 mM b-mercaptoethanol, 2 mM L-glutamine, 50 U mL–1 penicillin/streptomycin, and 4 ng mL–1 human recombinant basic fibroblast growth factor. By using surface marker antigens (SSEA-4, TRA-1-60, and TRA-1-81), we confirmed undifferentiated conditions of the used hES cells by immunocytochemistry. We assessed the developmental toxicity of well-known embryotoxic chemicals (cytosine arabinoside, 5-fluorouracil, hydroxyurea, and indomethacin) by expression of pluripotent ES cell markers (OCT-4, NANOG, endothelin receptor type B (EDNRB), secreted frizzled related protein 2(SFRP2), teratocarcinoma-derived growth factor 1 (TDGF1), and phosphatase, and tensin homologue (PTEN)) in different concentrations for up to 7 days. Expression of pluripotent ES cell markers were determined by quantitative real-time PCR. Data are presented as the mean ± standard error of the mean (s.e.m.), and were analysed with a one-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test. P-values <0.05 were considered to be statistically significant. Although expressions of the surface markers were not significantly affected, the embryotoxic chemicals influenced their response to pluripotent ES cell markers. Most of the pluripotent ES cell markers were down-regulated in dose-dependent manner following treatment with embryotoxic chemicals. After treatment with 5-fluorouracil, indomethacin, and penicillin G, we observed a remarkable convergence in the degree of up-regulation of development, cell cycle, and apoptosis-related genes by gene expression profiles using Affymetrix GeneChips (Santa Clara, CA, USA). Taken together, these results suggest that embryotoxic chemicals have cytotoxic effects, and modulate the expression of ES cell markers as well as development-, cell cycle-, and apoptosis-related genes that have pivotal roles in undifferentiated hES cells. Therefore, we suggest that hES cells may be useful for testing the toxic effects of chemicals that could affect the embryonic developmental stage.

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