Mesenchymal Stem Cells Derived from Human Adipose Tissues Favor Tumor Cell Growth in vivo

Abstract

Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical situations, due principally to their potential use in regenerative medicine and tissue engineering applications. However, the therapeutic application of MSCs remains limited, unless the favorable effects of MSCs for tumor growth in vivo and the long-term safety of the clinical applications of MSCs can be understood more thoroughly. In this study, MSCs derived from human adipose tissues (hASCs) together with tumor cells were transplanted subcutaneously or intracranially into BALB/c nude mice to observe tumor outgrowth. The results indicated that hASCs with H460 or U87MG cells promoted tumor growth in nude mice. Our histopathological analyses indicated that the co-injection of tumor cells with hASCs exerted no influence on the formation of intratumoral vessels. Co-culture of tumor cells with hASCs or the addition of conditioned medium (CM) from hASCs effected an increase in the proliferation of H460 or U87MG cells. Co-injection of hASCs with tumor cells effected an increase in tumor cell viability in vivo, and also induced a reduction in apoptotic cell death. CM from hASCs inhibited hydrogen peroxide-induced cell death in H460 or U87MG cells. These findings indicated that MSCs could favor tumor growth in vivo. Thus, it is necessary to conduct a study concerning the long-term safety of this technique before MSCs can be used as therapeutic tools in regenerative medicine and tissue engineering.

Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy

“…All these factors favor conditions that allow tumorsand might also allow tumor-associated MSCs in our model-to escape immune recognition and foster their proliferation and survival. A number of studies have shown enhancement of tumor growth and development, potentially through immunomodulatory and pro-angiogenic properties of MSCs, whereas others have shown no apparent effect of MSCs or have demonstrated inhibition of tumor growth and extended survival (15)(16)(17). Our results indicate that MSCs have no significant influence on the progression of gliomas in the brain.…”

“…Evidence suggests that MSCs may influence tumor progression in several tumor types (15)(16)(17). To determine the effect of engineered MSCs on glioma growth, we created a human glioma line Gli36-EGFRvIII expressing Fluc-DsRed2 (Gli36-EGFRvIII-FD) by transducing glioma cells with LV-Fluc-Dsred2.…”

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

“…Different MSC classes show tumor cell cytotoxicity, while others do not, which is in consensus with previous reports that proposed contradictory effects of MSCs on tumor cell proliferation [36,59,144]. There is a number of studies that employed cancer cell cultures and a part of them reported intensifying of cancer cell proliferation when MSCs are added [120,121], and some reported recordable MSCs anticancer activity [23,33,34,63,72,144,145]. Conventional anticancer drug screening in vitro is typically performed in the absence of additional cells from the tumor microenvironment, which can alter obtained results about antitumor activity in vivo.…”

“…But the anti-cancer properties of MSCs in humans are controversial because of still incomplete and limited human studies performed on small number of patients. The proposed use of MSCs in cancer therapies provoke strong disagreement in scientific community, due to opposite results for MSC promotion of tumor vascularization, promotion of cancer progression and the invasive tendency of tumors previously reported [28,[120][121][122]. In this contest, Li et al, 2011, inform about the dual role of human MSCs in tumor cell growth in vitro and in vivo.…”

Effect of the Multiple Intravenous Administration of Cultured Human Autologous Adipose-Derived Stem Cells on Tumor Biomarker Levels

“…In particular, it has to be considered seriously that concerns about the possibility of cancer development derived from cultured autologous adipose stem cells. The reasons for concerns about the possibility of cancer promotion by the administration of cultured adipose stem cells [8,9] are as follows: (1) genetic mutations may occur during the culturing process and (2) the growth factors secreted by stem cells may promote the growth of cancer cells and create a favorable environment for them. However, several reports have presented that stem cells inhibit cancer development [10][11][12], which suggests the importance of discerning the characteristics of cultured stem cells.…”