In Vitro Differentiation of Human Umbilical Cord Blood CD133+ Cells into Insulin Producing Cells in Co-Culture with Rat Pancreatic Mesenchymal Stem Cells.

In this article which was published in Cell J, Vol 17, No 2, Summer 2015, on pages 211-220, the authors found that Figures 3 and 4 had some errors that accidentally happened during organizing figures as well as because of mislabeling of some images and saving them in an incorrect folder. The following figures are corrected. The authors would like to apologies for any inconvenience caused.

Epigenetic reprogramming of primary pancreatic cancer cells counteracts their in vivo tumourigenicity.

Pancreatic ductal adenocarcinoma (PDAC) arises through accumulation of multiple genetic alterations. However, cancer cells also acquire and depend on cancer-specific epigenetic changes. To conclusively demonstrate the crucial relevance of the epigenetic programme for the tumourigenicity of the cancer cells, we used cellular reprogramming technology to reverse these epigenetic changes. We reprogrammed human PDAC cultures using three different techniques - (1) lentivirally via induction of Yamanaka Factors (OSKM), (2) the pluripotency-associated gene OCT4 and the microRNA mir-302, or (3) using episomal vectors as a safer alternative without genomic integration. We found that induction with episomal vectors was the most efficient method to reprogram primary human PDAC cultures as well as primary human fibroblasts that served as positive controls. Successful reprogramming was evidenced by immunostaining, alkaline phosphatase staining, and real-time PCR. Intriguingly, reprogramming of primary human PDAC cultures drastically reduced their in vivo tumourigenicity, which appeared to be driven by the cells' enhanced differentiation and loss of stemness upon transplantation. Our study demonstrates that reprogrammed primary PDAC cultures are functionally distinct from parental PDAC cells resulting in drastically reduced tumourigenicity in vitro and in vivo. Thus, epigenetic alterations account at least in part for the tumourigenicity and aggressiveness of pancreatic cancer, supporting the notion that epigenetic modulators could be a suitable approach to improve the dismal outcome of patients with pancreatic cancer.

In Vitro Differentiation of Human Umbilical Cord Blood CD133(+)Cells into Insulin Producing Cells in Co-Culture with Rat Pancreatic Mesenchymal Stem Cells.

OBJECTIVE: Pancreatic stroma plays an important role in the induction of pancreatic cells by the use of close range signaling. In this respect, we presume that pancreatic mesenchymal cells (PMCs) as a fundamental factor of the stromal niche may have an effective role in differentiation of umbilical cord blood cluster of differentiation 133(+) (UCB-CD133(+)) cells into newly-formed ß-cells in vitro. MATERIALS AND METHODS: This study is an experimental research. The UCB-CD133(+)cells were purified by magnetic activated cell sorting (MACS) and differentiated into insulin producing cells (IPCs) in co-culture, both directly and indirectly with rat PMCs. Immunocytochemistry and enzyme linked immune sorbent assay (ELISA) were used to determine expression and production of insulin and C-peptide at the protein level. RESULTS: Our results demonstrated that UCB-CD133(+)differentiated into IPCs. Cells in islet-like clusters with (out) co-cultured with rat pancreatic stromal cells produced insulin and C-peptide and released them into the culture medium at the end of the induction protocol. However they did not respond well to glucose challenges. CONCLUSION: Rat PMCs possibly affect differentiation of UCB-CD133(+)cells into IPCs by increasing the number of immature ß-cells.

cis-Dichlorodiamminoplatinum (II) glyconanoparticles by drug-induced ionic gelation technique targeted to prostate cancer: preparation, optimization and in vitro characterization.

BACKGROUND: Cancer stem cells (CSC) have been proposed as the reason of cancer relapse which are characterized mainly based on CD44+ phenotype with other supplementary markers. The aim of the present study is to fabricate cis-dichlorodiamminoplatinum (II) (CDDP) loaded glyconanoparticles using hyaluronic acid (HA) which is also known as the endogenous substrate for CD44 in vivo. METHODS: For this purpose, a drug-induced ionic gelation technique has been used to prepare CDDP-incorporated nanoparticles. To optimize the fabrication technique, stirring rate, stirring time, and HA/CDDP ratio have been selected as the main factors from other factors and subjected to face-centered central composite design for optimization purposes. The optimized nanoparticles were further characterized using different complementary methods including FTIR, SEM, AFM and DSC. To evaluate the biological effectiveness of CDDP nanoparticles release study, MTS assay, tumor cell clonogenicity and sphere formation assay have been performed as well. RESULTS: Spherical CDDP nanoparticles with Z-average approx. 150nm with low PdI were prepared by adjusting the selected variables. FTIR results indicated the presence of inclusion complexes between CDDP and HA which lead to preparing nanoparticles with high entrapment efficiency and drug content of 87.4 and 43.74 percentage respectively. In vitro release study showed a sustained release of CDDP up to 4 days, and cellular studies confirmed that nanoparticles formation keeps the anticancer activity of formulated CDDP while moderate increase in cancer stem cell suppression. CONCLUSION: It seems hyaluronic acid could be successfully exploited as carrier in cancer-targeted drug delivery with a look at targeting the CSCs.