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Knowledge about biological factors involved in exercise-induced angiogenesis is to date still scanty. The present study aimed to investigate the angiogenic stimulus of resistance exercise with and without superimposed whole-body vibrations. Responses to the exercise regimen before and after a 6-week training intervention were investigated in twenty-six healthy male subjects. Serum was collected at the initial and final exercise sessions and circulating levels of matrix metalloproteinases (MMP) -2 and -9, Vascular Endothelial Growth Factor (VEGF) and endostatin were determined via ELISA. Furthermore, we studied the proliferative effect of serum-treated human umbilical vein endothelial cells in vitro via BrdU-incorporation assay. It was found that circulating MMP-2, MMP-9, VEGF and endostatin levels were significantly elevated (P

Cardiac stem cell therapy has been proposed as a therapy option to treat the diseased myocardium. However, the low retention rate of transplanted single-cell suspensions remains a major issue of current therapy strategies. Therefore, the concept of scaffold-free cellular self-assembly into three-dimensional microtissues (3D-MTs) prior to transplantation may be beneficial to enhance retention and survival. We compared clinically relevant, human stem cell sources for their ability to generate 3D-MTs with particular regards to formation characteristics, proliferation-activity, viability and extracellular-matrix production. Single-cell suspensions of human bone marrow- and adipose tissue-derived mesenchymal stem cells (hBMMSCs and hATMSCs), Isl1(+) cardiac progenitors derived from human embryonic stem cells (hESC-Isl1(+) cells), and undifferentiated human induced pluripotent cells (hiPSCs) were characterized before to generate 3D-MTs using a hanging-drop culture. Besides the principal feasibility of cell-specific 3D-MT formation, a detailed head-to-head comparison between cell sources was performed using histology, immunocyto- and histo-chemistry as well as flow cytometry. Round-oval shaped and uniform 3D-MTs could be successfully generated from all cell types starting with a loose formation within the first 24 h that fully stabilized after 3 days and resulting in a mean 3D-MT diameter of 194.56 ± 18.01 μm (hBMMSCs), 194.56 ± 16.30 μm (hATMSCs), 159.73 ± 19.20 μm (hESC-Isl1(+) cells) and 120.95 ± 7.97 μm (hiPSCs). While all 3D-MTs showed a homogenous cell distribution, hiPSC-derived 3D-MTs displayed a compact cell formation primarily located at the outer margin. hESC-Isl1(+) and hiPSC-derived 3D-MTs maintained their proliferation-activity which was rather limited in the MSC-based 3D-MTs. All four 3D-MT types revealed a comparable viability in excess of 70% and showed a cell-specific expression profile being comparable to their single-cell counterparts. Extracellular matrix (ECM) production during 3D-MT formation was observed for all cell-specific 3D-MTs, with hiPSC-derived 3D-MTs being the fastest one. Interestingly, ECM distribution was homogenous for hATMSC- and hiPSC-based 3D-MTs, while it appeared to be primarily concentrated within in the center of hESC-Isl1(+) and hBMMSC-based 3D-MTs. The results of this head-to-head comparative study indicated that 3D-MTs can be successfully generated from hESC-derived Isl1(+) cells, hiPSCs and MSC lines upon hanging drop culture. Cell-specific 3D-MTs displayed sufficient viability and instant ECM formation. The concept of 3D-MT in vitro generation prior to cell transplantation may represent a promising delivery format for future strategies to enhance cellular engraftment and survival.

BACKGROUND In vivo confocal microscopy (IVCM) enables large-field in vivo examination of the corneal endothelium and corneal precipitates. Keratic precipitates (KP) are prominent features of Fuchs Heterochromic uveitis syndrome (FHUS). The aim of this study was to investigate the effect of KP on the corneal endothelium. PATIENTS AND METHODS Eight patients with clinically diagnosed FHUS and KP between July 2007 and May 2008 underwent slit lamp examination and IVCM. KP (shape, area), endothelial cell count and percentage of hexagonal cells were measured and compared with an age-matched control group and with not affected healthy contralateral eyes. RESULTS The age of participants ranged between 26 and 67 years. KP had a diameter ranging between 37 to 217 microm (mean 137 microm) with an average area of KP of 5630 microm (2). The mean endothelial cell count in the study group was 2541 +/- 299 cells/mm (2), 2722 +/- 312 cells/mm (2) in the control group (p = 0,18) and 2397 +/- 192 cells/mm (2) in not affected contralateral eyes (p = 0.17). The percentage of hexagonal cells was 59.1 % in FHUS study group and 69.1 % in the control group (p = 0.0002) and 68.6 % in not affected contralateral eyes (p = 0.0495). CONCLUSIONS KP in FHUS cause a focal damage of endothelial cells reflected in a decreased percentage of healthy hexagonal cells. The degree of endothelial cell damage seems to be low as it does not lead to a significant reduction in the endothelial cell count.