Mesenchymal stem cell-like cells from children foreskin inhibit the growth of SGC-7901 gastric cancer cells
Introduction
Mesenchymal stem cells (MSCs) have become an attractive therapeutic tool for regenerative medicine, cellular immunotherapy and gene therapy (Aggarwal and Pittenger, 2005, Wulf et al., 2006), because of their unique characteristics, multi-differentiation potentials and immunomodulatory functions. MSCs can be easily isolated and cultured, and induced to differentiate into distinct types, such as osteoblasts, chondroblasts, adipocytes, hepatocyte-like cells and myoblasts (Pittenger et al., 1999, Schwartz et al., 2002, Xu et al., 2004). MSCs are able to be isolated from a wide variety of tissues, including bone marrow, adipose tissue, skeletal muscle, cord blood, placenta and umbilical cord (Deans and Moseley, 2000, Jiang et al., 2002, Qiao et al., 2008). Recently, some reports demonstrate that skin could serve as a source of stem cells (Blanpain and Fuchs, 2006, Fernandes et al., 2004). The skin-derived fibroblasts are of broad differentiation potentials, express MSC-like immunophenotype and possess immunosuppressive properties similar to human bone marrow MSCs (hBM-MSCs) (Lavoie et al., 2009, Toma et al., 2005, Wada et al., 2011). These findings provide evidence that skin can serve as a new source for adult stem cells and might be of great potential for future therapeutic applications. Human foreskin tissue is the main skin source of MSCs, because it is abundant, inexpensive and can be obtained through noninvasive procedures that do not pose any ethical concerns. More recently, other fibroblast-like cells originated from skin tissue have been reported and these cells can support the self-renewal and pluripotency of human embryonic stem cells (hESCs) (Mamidi et al., 2011, Unger et al., 2009), which hold great promise for regenerative medicine for their ability to differentiate into almost all cell types, such as bone tissue, vascular cells and heart regeneration (Jiang et al., 2012, Marolt et al., 2012, Volz et al., 2012). HFMSCs can also different into putative endothelial-like cells and islet-like cell clusters in vitro (Bi et al., 2010, Vishnubalaji et al., 2012). However, the limitations such as low isolation rate and different differentiation properties make the search for skin tissue source to be continued.
We previously demonstrated that MSCs derived from bone marrow favor tumor growth through secreted soluble signaling molecules (Zhu et al., 2006, Zhu et al., 2011, Zhu et al., 2012). Other reports also prove that MSCs facilitate tumor growth and metastasis (Tsukamoto et al., 2012). In contrary, other researchers hold that MSCs play a suppressive effect in tumor occurrence and growth. IFN-β expressing MSCs can inhibit primary breast cancer growth and reduce pulmonary and hepatic metastases (Ling et al., 2010). MSCs have also been reported to inhibit hepatocellular carcinoma metastasis (Li et al., 2010). The report from Menen et al. (2012) demonstrates that extracellular matrix of foreskin fibroblasts in culture inhibits the metastasis of circulating human prostate cancer cells. In this study we optimize the method to obtain hFMSCs and explore the effect of hFMSCs on human gastric cancer SGC-7901 cells.
Section snippets
Cell lines
Human gastric adenocarcinoma SGC-7901 cells were purchased from Cell Bank, Type Culture Collection Committee Chinese Academy of Sciences. Human colon cancer SW480 cells were purchased from ATCC. All cell lines were cultured in DMEM supplemented with 10% FBS at 37 °C in 5% CO2.
Isolation of mesenchymal stem cell-like cells from human foreskin samples
Children foreskin samples were obtained from the Affiliated Renmin Hospital of Jiangsu University with informed consent from their legally authorized representatives (LARs). HFMSCs were isolated, cultured, and characterized
Isolation and expansion of hFMSCs
After 5 days of primary culture, the epithelial-like cells and fibroblast-like cells migrated out of the foreskin tissues and adhered to the plastic surface (Fig. 1Aa). Approximately 10 days after plating, the fibroblast-like cells began to form colonies while the epithelial-like cells did not proliferate (Fig. 1Ab). The well developed colonies of fibroblast-like cells were trypsinized and passaged into a new flask for further expansion and the medium changed every 3 days. The results showed that
Discussion
MSCs from distinct tissues may show different characteristics and application prospective (Cavallo et al., 2011). Children foreskin, as a part of the skin, provides a possible source for MSCs from skin. The previous investigations of MSCs from epidermis and dermis suggest that dermis may represent a considerable reservoir for adult stem cells (Hoogduijn et al., 2006, Shi et al., 2006). Skin-derived stem cells provide basis for autologous transplantation to treat a number of skin-related
Conflicts of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (grant no. 81270214) and the Scientific Research Foundation of Jiangsu University (grant no. 11JGD0090).
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