Priming with a Combination of FGF2 and HGF Restores the Impaired Osteogenic Differentiation of Adipose-Derived Stem Cells.

Classical aging-associated diseases include osteoporosis, diabetes, hypertension, and arthritis. Osteoporosis causes the bone to become brittle, increasing fracture risk. Among the various treatments for fractures, stem cell transplantation is currently in the spotlight. Poor paracrine/differentiation capacity, owing to donor age or clinical history, limits efficacy. Lower levels of fibroblast growth factor 2 (FGF2) and hepatocyte growth factor (HGF) are involved in cell repopulation, angiogenesis, and bone formation in the elderly ADSCs (ADSC-E) than in the young ADSCs (ADSC-Y). Here, we study the effect of FGF2/HGF priming on the osteogenic potential of ADSC-E, determined by calcium deposition in vitro and ectopic bone formation in vivo. Age-induced FGF2/HGF deficiency was confirmed in ADSCs, and their supplementation enhanced the osteogenic differentiation ability of ADSC-E. Priming with FGF2/HGF caused an early shift of expression of osteogenic markers, including Runt-related transcription factor 2 (Runx-2), osterix, and alkaline phosphatase (ALP) during osteogenic differentiation. FGF2/HGF priming also created an environment favorable to osteogenesis by facilitating the secretion of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF). Bone tissue of ADSC-E origin was observed in mice transplanted with FGF/HGF-primed ADSC-E. Collectively, FGF2/HGF priming could enhance the bone-forming capacity in ADSC-E. Therefore, growth factor-mediated cellular priming can enhance ADSC differentiation in bone diseases and thus contributes to the increased efficacy in vivo.

Manual reduction of torsion of an intrascrotal appendage under ultrasonographic monitoring.

OBJECTIVE: The purpose of this study was to evaluate the feasibility and safety of manual reduction of torsion of an intrascrotal appendage under ultrasonographic monitoring. METHODS: Fifteen boys with torsion of an intrascrotal appendage, confirmed by scrotal ultrasonography and clinical status, were included in the study. The boys were 6 to 13 years old (mean age, 9 years). They all had painful, unilateral swelling of the scrotum and a palpable, tender nodule on physical examination. Scrotal ultrasonography indicated a single, variably echoic mass corresponding to the intrascrotal appendage. The mass was avascular according to Doppler ultrasonography. Thirteen boys underwent manual reduction under ultrasonographic monitoring. We tried to pull and release the swollen appendage in 8 patients and gently squeezed the appendage in 5. The procedure was considered successful when ultrasonography showed reperfusion in the appendage and the patients stated complete relief of scrotal pain. In 14 boys, follow-up scrotal ultrasonography was performed after the manual reduction. RESULTS: Successful reduction was obtained in 12 (80.0%) of 15 boys. Only 1 boy was regarded as having reduction failure; this patient had intractable pain after the trial reduction, and ultrasonography showed transient vascular flow that promptly disappeared in the appendage. On follow-up ultrasonography, the maximal diameter +/- SD of the intrascrotal appendages significantly decreased from 6.1 +/- 1.2 to 4.0 +/- 1.3 (P=.005) in 11 patients with successful reduction. CONCLUSIONS: Manual reduction under ultrasonographic monitoring seems to be a feasible and effective method for the treatment of torsion of an intrascrotal appendage to immediately relieve pain.