Background. Mesenchymal stem cells (MSCs), also known as multipotent progenitor cells, release several factors that support cell survival and enhance wound healing. We hypothesized that MSC-secreted molecules would induce a trophic effect in pancreatic islet culture conditions. Methods. Pancreatic islets were co-cultured with MSCs, and ADP/ATP ratios, glucose stimulated insulin secretion (GSIS), and DNA fragmentation were evaluated to measure islet quality and viability in vitro. The induction of signal molecules related to the control of survival, function, and angiogenesis was also analyzed. Cell quality assays, DNA fragmentation assays, and islet transplantation into streptozotocin-induced diabetic mice were performed using MSC-conditioned medium (CM)–cultured islets. Furthermore, we identified soluble molecules within MSC-CM. Results. Islets co-cultured with MSCs demonstrated lower ADP/ATP ratios, and higher GSIS indexes and viability. Furthermore, co-cultured islets revealed higher levels of anti-apoptotic signal molecules (X-linked inhibitor of apoptosis protein, Bcl-xL, Bcl-2, and heat shock protein-32) and demonstrated increased vascular endothelial growth factor receptor 2 and Tie-2 mRNA expression and increased levels of phosphorylated Tie-2 and focal adhesion kinase protein. Islets cultured in MSC-CM demonstrated lower ADP/ATP ratios, less apoptosis, and a higher GSIS indexes. Diabetic mice that received islet transplants (200 islet equivalent) cultured in MSC-CM for 48 hr demonstrated significantly lower blood glucose levels and enhanced blood vessel formation. In addition, interleukin-6, interleukin-8, vascular endothelial growth factor-A, hepatocyte growth factor, and transforming growth factor-β were detected at significant levels in MSC-CM. Conclusions. These results suggest that the trophic factors secreted by human MSCs enhance islet survival and function after transplantation.
1 March 2005 in Journal of Clinical Gastroenterology
To compare the efficacy of radiofrequency ablation (RFA) and surgical resection in a group of patients with a Child-Pugh score of 5 and a single HCC less than 4 cm in diameter. Radiofrequency ablation (RFA) has become a popular method for treatment of hepatocellular carcinoma (HCC) and has been applied as an alternative primary therapy to surgical resection. We compared outcomes for 148 patients treated with RFA (n = 55) and those treated surgically (n = 93). The rate of local recurrence among patients in the RFA group was significantly higher than in the surgery group (P = 0.005), while the incidence of remote recurrence was similar between the two groups (P = 0.30). The cumulative 1- and 3-year overall survival rates (P = 0.24) and the cumulative 1- and 3-year recurrence-free survival rates (P = 0.54) were not significantly different between the two groups. Despite a higher rate of local recurrence, RFA was found to be as effective as surgical resection for the treatment of single small HCC in patients with well-preserved liver function, in terms of the incidence of remote recurrence and the patients' likelihood of achieving overall and/or recurrence-free survival.
The role of the radiofrequency ablation (RFA) in treatment of solitary liver metastasis has not been established yet. Both hepatic resection (HR) and RFA have been used increasingly in the treatment of colorectal liver metastases. A systemic review was performed to determine the impact of treatment modality of solitary liver metastasis on recurrence patterns, disease-free survival, and overall survival (OS) rates. Solitary liver metastases were treated by HR in 116 patients (75.8%) and 37 patients (24.2%) were treated with RFA. Prognostic factors, recurrence rate, recurrence patterns, and survival rates were analyzed. The cumulative 3-year and 5-year local recurrence free survival rates were markedly higher in the HR group (88.0% and 84.6%) as compared with those in the RFA group [53.3% and 42.6%, respectively (P≤0.001)]. The 5-year OS rate was lower in the RFA group as compared with the HR group without statistical significance (5-year OS, 65.7% in the HR, 48.5% in the RFA group, P=0.227). Despite of higher local recurrence rate, RFA may be considered as a therapeutic option for patients who are considered unsuitable for conventional surgical treatment. Randomized prospective controlled trials comparing the therapeutic outcome of RFA and HR are definitely warranted.