PMID- 19207272 OWN - NLM STAT- MEDLINE DCOM- 20090814 LR - 20211020 IS - 1743-6109 (Electronic) IS - 1743-6095 (Print) IS - 1743-6095 (Linking) VI - 6 IP - 4 DP - 2009 Apr TI - Fibroblast growth factor 2 promotes endothelial differentiation of adipose tissue-derived stem cells. PG - 967-979 LID - S1743-6095(15)32480-2 [pii] LID - 10.1111/j.1743-6109.2008.01172.x [doi] AB - INTRODUCTION: Adipose tissue-derived stem cells (ADSC) could potentially restore endothelial function in vasculogenic erectile dysfunction (ED). The mechanism for ADSC endothelial differentiation remained unidentified. AIM: To test whether ADSC could differentiate into endothelial cells in the penis and to identify the underlying mechanism of ADSC endothelial differentiation. METHODS: For in vivo endothelial differentiation, ADSC were labeled with bromodeoxyuridine (BrdU), injected into rat corpora cavernosa, and localized by immunofluorescence and phase-contrast microscopy. For in vitro endothelial differentiation, ADSC were grown in endothelial growth medium 2 (EGM2), stained for endothelial markers CD31, von Willebrand Factor (vWF), and endothelial nitric oxide synthase (eNOS), and assessed for the ability to form tube-like structures in Matrigel and to endocytose acetylated low-density lipoprotein (Ac-LDL). To identify factors that promote ADSC endothelial differentiation, ADSC were grown in various media, each of which contained a specific combination of supplemental factors and assessed for LDL-uptake. PD173074, a selective inhibitor of fibroblast growth factor 2 (FGF2) receptor, was used to confirm the importance of FGF2 signaling for ADSC endothelial differentiation. MAIN OUTCOME MEASURES: In vivo endothelial differentiation was assessed by immunofluorescence microscopy. In vitro endothelial differentiation was assessed by immunofluorescence, Matrigel tube formation, and Ac-LDL uptake. RESULTS: Injected ADSC were localized to the sinusoid endothelium, some of which stained positive for both BrdU and endothelial antigen rat endothelial cell antigen. ADSC proliferated at a faster rate in EGM2 than in standard DMEM, expressed endothelial markers CD31, vWF, and eNOS, formed tube-like structures in Matrigel, and endocytosed Ac-LDL. These properties were greatly diminished when ADSC were grown in the absence of FGF2 but were unaffected when grown in the absence of vascular endothelial growth factor, insulin-like growth factor, or epidermal growth factor. Furthermore, ADSC displayed similar endothelial properties when grown in FGF2-supplemented basic medium as in EGM2. Finally, blockade of FGF2 signaling with PD173074 abrogated ADSC endothelial differentiation. CONCLUSIONS: ADSC could differentiate into endothelial cells in the penis. FGF2 signaling mediates ADSC endothelial differentiation. FAU - Ning, Hongxiu AU - Ning H AD - University of California, School of Medicine, Knuppe Molecular Urology Laboratory-Department of Urology, San Francisco, California, USA. FAU - Liu, Gang AU - Liu G AD - University of California, School of Medicine, Knuppe Molecular Urology Laboratory-Department of Urology, San Francisco, California, USA. FAU - Lin, Guiting AU - Lin G AD - University of California, School of Medicine, Knuppe Molecular Urology Laboratory-Department of Urology, San Francisco, California, USA. FAU - Yang, Rong AU - Yang R AD - University of California, School of Medicine, Knuppe Molecular Urology Laboratory-Department of Urology, San Francisco, California, USA. FAU - Lue, Tom F AU - Lue TF AD - University of California, School of Medicine, Knuppe Molecular Urology Laboratory-Department of Urology, San Francisco, California, USA. FAU - Lin, Ching-Shwun AU - Lin CS AD - University of California, School of Medicine, Knuppe Molecular Urology Laboratory-Department of Urology, San Francisco, California, USA. Electronic address: cslin@urology.ucsf.edu. LA - eng GR - R01 DK069655-05/DK/NIDDK NIH HHS/United States GR - R01 DK069655/DK/NIDDK NIH HHS/United States GR - R37 DK045370/DK/NIDDK NIH HHS/United States GR - R01 DK051374-05/DK/NIDDK NIH HHS/United States GR - R37 DK045370-13/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080204 PL - Netherlands TA - J Sex Med JT - The journal of sexual medicine JID - 101230693 RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (von Willebrand Factor) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Adipose Tissue/*metabolism MH - Animals MH - Bromodeoxyuridine/administration & dosage MH - *Cell Differentiation MH - Cell Proliferation MH - Endothelium, Vascular/immunology/*metabolism/pathology MH - Erectile Dysfunction/immunology/pathology/*physiopathology MH - Fibroblast Growth Factor 2/*metabolism MH - Fluorescent Antibody Technique MH - In Vitro Techniques MH - Injections MH - Male MH - Nitric Oxide Synthase/metabolism MH - Platelet Endothelial Cell Adhesion Molecule-1/immunology MH - Rats MH - Rats, Sprague-Dawley MH - Staining and Labeling MH - Stem Cells/*metabolism MH - von Willebrand Factor/metabolism PMC - PMC2893032 MID - NIHMS213732 EDAT- 2009/02/12 09:00 MHDA- 2009/08/15 09:00 PMCR- 2010/06/28 CRDT- 2009/02/12 09:00 PHST- 2009/02/12 09:00 [entrez] PHST- 2009/02/12 09:00 [pubmed] PHST- 2009/08/15 09:00 [medline] PHST- 2010/06/28 00:00 [pmc-release] AID - S1743-6095(15)32480-2 [pii] AID - 10.1111/j.1743-6109.2008.01172.x [doi] PST - ppublish SO - J Sex Med. 2009 Apr;6(4):967-979. doi: 10.1111/j.1743-6109.2008.01172.x. Epub 2008 Feb 4.