[Research Progress on TKI Resistance of CML Cells Mediated by MSC through CXCL12/CXCR4 Axis].

Although the tyrosinekinase inhibitors (TKI) displayed a significant curative effect on chronic myeloid leukemia (CML), but the drug resistance in treatment course of this disease still can not be avoided. Studies recently have shown that the mesenchymal stem cells (MSC) can induce CML cells to resist TKI therapy by CXCL12/CXCR4 axis from multiple aspects, such as the directional migration of CML cells, adherence to marrow cavity, the mediation of cell protective dormancy, activations of numerous survival signaling pathways, the suppression of mitochondrial-dependent apoptosis and the up-regulated expression of BCL-6. The combination of TKI and CXCR4 antagonists will be a novel treatment strategy to raise the genetic cure rate of CML. In this article, the pathways of drug resistance, pathways of sensitivity to CXCL12 and pathways of CML cell adherence to marrow cavity in CML cells mediated by MSC were reviewed.

Lentiviral-mediated overexpression of homeobox A4 by human umbilical cord mesenchymal stem cells repairs full-thickness skin defects.

A number of types of stem cells have been shown to be effective in wound repair. In the present study the effect of homeobox A4 (HOXA4) overexpression by human umbilical cord mesenchymal stem cells (hUMSCs) on full­thickness skin repair was evaluated. Isolated hUMSCs were transfected with a lentivirus expressing HOXA4 and cultured for 21 days. Expression of the epidermal cell­specific markers, cytokeratins 14 and 18, was detected by immunohistochemistry and flow cytometry. Full­thickness skin defects (1.5 cm x 1.5 cm) were made on the backs of 45 nude mice, which were randomly divided into the following three treatment groups: Collagen membrane with lenti­HOXA4 hUMSC seed cells; collagen membrane with lentivirus expressing green fluorescent protein; and collagen membrane alone. On days 7, 14 and 21 following transplantation, tissue samples were harvested and examined by histology and western blot analysis. Flow cytometry showed that the transfection efficiency was 95.41% at a multiplicity of infection of 100, and that the lenti­HOXA4 hUMSCs differentiated into epidermal cells, expressing cytokeratins 14 and 18. In addition, re­epithelialization of wounds treated with lenti­HOXA4 hUMSCs was significantly greater than that in the control groups in the first week. By week three the epidermis was significantly thicker in the lenti­HOXA4 group than the control groups. Thus, transplantation of hUMSCs modified with Ad­HOXA4 promoted wound healing.

N-acetyl cysteine inhibits human signet ring cell gastric cancer cell line (SJ-89) cell growth by inducing apoptosis and DNA synthesis arrest.

BACKGROUND AND AIMS: In this study, we investigated the inhibitory effects of N-acetyl cysteine (NAC) on the growth of the human signet ring cell from the gastric-cancer cell line SJ-89 , via the induction of apoptosis and the arrest of DNA synthesis. MATERIALS AND METHODS: SJ-89 cells were regularly incubated in the presence of NAC at 5, 10 and 20 mmol/l, and with IMDM as untreated control. Trypan blue-dye exclusion analysis and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay were applied to detect cell proliferation. Apoptotic morphology was observed by electron microscopy. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay were performed to detect NAC-triggered apoptosis. RESULTS: NAC could inhibit proliferation of human gastric cancer SJ-89 cells in a dose-dependent and time-dependent manner. The growth curve showed suppression by 15.8, 37.6 and 66.3% following 72 h of NAC treatment at 5, 10 and 20 mmol/l, respectively, similar to the findings of 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. DNA synthesis was evidently reduced by 25, 39 and 91% after 24 h NAC treated at 20 mmol/l and 5 days at 10 and 20 mmol/l, respectively. Cell growth was inhibited by 100% with the treatment of 20 mmol/l NAC on day 6. NAC-treated SJ-89 cells were characterized by typical apoptotic alterations, including morphological changes by electron microscopy, typical apoptotic sub-G1 peaking observed by flow cytometry and increase of apoptotic cells with the elevation of the concentration of NAC in a clearly dose-dependent manner by TUNEL assay. Electrophoresis analysis showed typical 'DNA ladder'. CONCLUSION: The data above implicated that NAC inhibits human gastric-cancer SJ-89 cell growth by inducing apoptosis and DNA synthesis arrest. Although the exact mechanisms involved in NAC-induced apoptosis have not been known up to now, the ability to induce apoptosis in a tumor-cell population within 48 h is worth noting. It is also noteworthy that NAC can selectively inhibit the growth of tumor cells. Further studies are needed to elucidate the mechanisms.