Mesenchymal stem cell-like cells from children foreskin inhibit the growth of SGC-7901 gastric cancer cells

Abstract

Mesenchymal stem cells (MSCs) become a research hotspot in recent years because of their roles in regenerative medicine and tissue injury repair. However, the limited source for MSCs hampers its clinical application. In this study, we isolated and identified human mesenchymal stem cell-like cells from foreskin (hFMSCs) by explant culture. HFMSCs had similar morphology and immunophenotype to that of human bone marrow derived-mesenchymal stem cells. HFMSCs formed colonies after 9 days of inoculation and could be propagated for more than 50 passages. HFMSCs had a normal karyotype and high G0/G1 phase independent of passage number. Further, hFMSCs could be induced to differentiate into osteocytes and adipocytes. We found that the growth of SGC-7901 (human gastric adenocarcinoma) cells could be suppressed by simultaneous injection of hFMSCs in vivo. HFMSCs also inhibited SGC-7901 cell proliferation in vitro. HFMSC co-injection resulted in a decrease in PCNA-positive and an increase in apoptotic tumor cells. HFMSCs derived conditioned medium inhibited the expression of BCL-2 while increased the expression of BAX and caspase-3 in SGC-7901 cells. Taken together, our findings suggest that children foreskin is a new source for MSCs and hFMSCs could inhibit gastric cancer cell growth both in vitro and in vivo.

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.