Inhibitory and Apoptotic Effects of Mannan-Mitomycin C Conjugate Against Transitional Cell Carcinoma and Normal Mouse Fibroblasts.

BACKGROUND: Many studies have shown the anticancer effects of mannan and mitomycin C on tumor cells. In this regard, the aim of this study was to investigate the inhibitory and apoptotic effects of a mannan-mitomycin-C conjugate on transitional cell carcinoma (TCC) and normal mouse L929 fibroblast cells. METHODS: The conjugate was synthesized according to previous studies. Both cell lines were cultured and the cytotoxic and apoptotic effects of the compounds in different concentrations were assessed using MTT and flow cytometry, respectively. The mannan-mitomycin C conjugate inhibited proliferation of both cell lines in time and concentration -dependent manners. RESULTS: The conjugate inhibited TCC cell proliferation more than that of L929 cells. Mitomycin C alone inhibited proliferation of both cell lines in both time and concentration -dependent manners, and the effect was greater on L929 than on TCC cells. Mannan had a relatively low inhibitory effect on TCC and no significant effect on L929 cells. The percentage of apoptosis was greater in TCCs than in L929 cells at the highest concentration of conjugate. Mitomycin C induced apoptosis more extensively in L929 cells than in TCC cells at 25 and 400 µg/ml. The effect of mannan was similar on both cell lines. CONCLUSION: The mannan-mitomycin C conjugate has greater inhibitory and apoptotic effects on TCC than on L929 cells and may inhibit TCC.

Bone morphogenetic protein-7 incorporated polycaprolactone scaffold has a great potential to improve survival and proliferation rate of the human embryonic kidney cells.

Renal failures treatment has been faced with several problems during the last decades. Kidney tissue engineering has been created many hopes to improve treatment procedures with scaffold fabrication that can modulate kidney cells/stem cells migration to the lesion site and increase the survival of these cells at that site with imitating the role of the kidney extracellular matrix. In this study, bone morphogenetic protein-7 (BMP7) as a vital factor for kidney development and regeneration was incorporated in the polycaprolactone (PCL) nanofibers and after morphological, mechanical, and biocompatible characterization, proliferation, and survival of the human embryonic kidney cells (HEK) were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and gene expression while cultured on scaffolds. Mechanical properties of the PCL nanofibers modulated after combining with BMP7 and hydration degree, protein adsorption and cell adhesion were enhanced in PCL-BMP7 compared to the pure PCL. Proliferation rate and growth increased significantly in HEK cells cultured on PCL-BMP7 when compared with that of PCL and tissue culture plate, whereas these data were also confirmed via significant decrease in apoptotic genes expression level in HEK cell cultured on PCL-BMP7. According to the results, PCL-BMP7 demonstrated positive effects on the survival and proliferation rate of the kidney cells and showed has also a great potential to use as a bioimplant for kidney tissue engineering applications.

Adipose-derived stem cells-conditioned medium improved osteogenic differentiation of induced pluripotent stem cells when grown on polycaprolactone nanofibers.

Considering that the common osteogenic growth factors cannot be transplanted with stem cells to the patients, many studies are underway to find a replacement for these factors. Recently, it has been determined that mesenchymal stem cell (MSC)-derived conditioned medium (CM) contains effective factors in the bone formation process. In the current study, the synergistic effect of adipose-derived MSC's CM, and polycaprolactone (PCL) scaffold was investigated on the osteogenic differentiation potential of human induced pluripotent stem cells (iPSCs). After scaffold fabrication by electrospinning and characterization by scanning electron microscopy, iPSCs proliferation in the presence of CM, PCL, and both was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide. Then, iPSCs osteogenic differentiation was investigated while cultured on tissue culture plate and PCL under CM compared with the osteogenic medium using alizarin red staining, calcium content, alkaline phosphatase activity and gene and protein expression analysis. Proliferation rate of the iPSCs was increased while cultured under CM and its effect was synergistically enhanced by culture on PCL. Evaluation of the osteogenic markers was showed CM alone could induce osteogenic differentiation into the iPSCs and this potential was significantly increased while combined with PCL nanofibrous scaffold. According to the results, it was demonstrated that CM has an osteogenic induction property almost the same of the common osteogenic medium and it can also be used potentially with stem cells when transplant to the patients. CM can also help by prolonging cell survival at the site of the defect as well as accelerating healing process.