Lipofilling is a widely used technique in plastic and reconstructive surgery, but its long-term success is often limited by unpredictable fat graft resorption. Optimizing the adipogenic environment th Show more
Lipofilling is a widely used technique in plastic and reconstructive surgery, but its long-term success is often limited by unpredictable fat graft resorption. Optimizing the adipogenic environment through bioactive factors may enhance graft survival and volume retention. This study investigates the adipogenic potential of Hypoxia Preconditioned Serum (HPS) and Platelet-rich Plasma (PRP), in comparison to normal serum (NS). Cytokine profiles of HPS, PRP, and NS from 10 donors were analyzed. Human preadipocytes (n = 3) were cultured with low (10%) and high (40%) concentrations of these secretomes. Proliferation, cytotoxicity (LDH assay), lipid droplet formation (Oil Red O staining), and gene expression (qPCR) of adipogenic markers (PPARgamma, C/EBPalpha, FABP4, Adiponectin, LPL) were assessed after 2 and 4 days. HPS contained significantly higher levels of Adiponectin, IGF-1, bFGF, VEGF-A, and PDGF-BB compared with PRP and NS, while Leptin was lower in HPS and PRP than in NS. All conditions increased proliferation on day 4, with the highest cell counts in NS-40%. No treatment-related cytotoxicity was observed. HPS-40% induced the strongest adipogenic differentiation, evidenced by increased lipid droplet formation and upregulation of all measured adipogenic genes by day 4. These findings suggest that HPS enhance the proliferation, survival, and differentiation of preadipocytes. Validation in Show less
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; Show more
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene. Show less