Neural Induction Potential and MRI of ADSCs Labeled Cationic Superparamagnetic Iron Oxide Nanoparticle In Vitro.

Magnetic resonance imaging (MRI) combined with contrast agents is believed to be useful for stem cell tracking in vivo, and the aim of this research was to investigate the biosafety and neural induction of SD rat-originated adipose derived stem cells (ADSCs) using cationic superparamagnetic iron oxide (SPIO) nanoparticle which was synthesized by the improved polyol method, in order to allow visualization using in vitro MRI. The scan protocols were performed with T2-mapping sequence; meanwhile, the ultrastructure of labeled cells was observed by transmission electron microscopy (TEM) while the iron content was measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES). After neural induction, nestin and NSE (neural markers) were obviously expressed. In vitro MRI showed that the cationic PEG/PEI-modified SPIO nanoparticles could achieve great relaxation performance and favourable longevity. And the ICP-AES quantified the lowest iron content that could be detected by MRI as 1.56~1.8 pg/cell. This study showed that the cationic SPIO could be directly used to label ADSCs, which could then inductively differentiate into nerve and be imaged by in vitro MRI, which would exhibit important guiding significance for the further in vivo MRI towards animal models with neurodegenerative disorders.

Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo.

AIM: To investigate the anticancer effect of a recombinant adenovirus-mediated p53 (rAd-p53) combined with 5-fluorouracil (5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of rAd-p53 in reversal of 5-FU resistance. METHODS: Nude mice bearing human colon cancer SW480/5-FU (5-FU resistant) were randomly assigned to four groups (n = 25 each): control group, 5-FU group, rAd-p53 group, and rAd-p53 + 5-FU group. At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were randomly selected from each group and sacrificed using an overdose of anesthetics. The tumors were removed and the protein expressions of p53, protein kinase C (PKC), permeability-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) (Western blot) and apoptosis (TUNEL) were determined. RESULTS: The area ratios of tumor cell apoptosis were larger in the rAd/p53 + 5-FU group than that in the control, 5-FU and rAd/p53 groups (P < 0.05), and were larger in the rAd/p53 group than that of the control group (P < 0.05) and the 5-FU group at more than 48 h (P < 0.05). The p53 expression was higher in the rAd/p53 and the rAd/p53 + 5-FU groups than that of the control and 5-FU groups (P < 0.05), and were higher in the rAd/p53 + 5-FU group than that of the rAd/p53 group (P < 0.05). Overexpression of PKC, P-gp and MRP1 was observed in the 5-FU and control groups. In the rAd/p53 + 5-FU group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups (P < 0.05), and the expression of PKC was lower than that of the control, 5-FU and rAd/p53 groups at more than 48 h (P < 0.05). In the rAd/p53 group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups at more than 48 h (P < 0.05), and the expression of PKC was lower than that of the control and 5-FU groups at more than 120 h (P < 0.05). CONCLUSION: 5-FU combined with rAd-p53 has a synergistic anticancer effect in SW480/5-FU (5-FU resistance), which contributes to reversal of 5-FU resistance.