Mesenchymal stem cells (MSCs) represent a promising new approach to the treatment of several diseases that are associated with dismal outcomes. including the absence of long term follow-up and lack of adequate screening methods to detect formation of new tumors. Through discussions of the possible oncogenic and tumor-supporting mechanisms of MSCs directions for future research are identified which may eventually facilitate the future clinical Vitexin translation of MSCs for the treatment of cancer and other diseases. due to their fibroblast-like morphology and the propensity to form colonies in culture . They are now referred to as or MALIGNANT TRANSFORMATION Considerable expansion is often necessary to achieve adequate numbers of MSCs for restorative purposes [7-9]. This development phase is the 1st point at which MSCs become susceptible to malignant transformation as Abcc4 demonstrated in Fig. (2a). Rubio and downregulation of p16 although this trend was not observed after only 6 to 8 8 weeks in tradition . Wang tradition of human being bone marrow-derived MSCs generates a sub-population of cells with high levels of telomerase activity chromosomal aneuploidy and translocations that are capable of forming tumors in multiple organs in NOD/SCID mice . These findings were not reproduced inside a subsequent study in which chromosomal abnormalities were absent and normal telomere shortening was observed in human being bone marrow-derived MSCs Vitexin that were propagated to senescence or 25 passages . Because the results of such experiments conflict with one another and because Vitexin available research on characteristics of MSCs is limited the possibility of malignant transformation remains highly controversial. Future studies which employ standardized isolation protocols for MSCs will therefore be needed to elucidate the poorly understood potential for malignant transformation during the expansion phase . Figure 2 Mechanisms by which mesenchymal stem cells may undergo carcinogenic transformation. (A) Transformation may occur by the outgrowth of a sub-population of cells that proliferates more favorably in culture conditions. (B) Interactions between tumor stroma … MESENCHYMAL STEM CELLS MIGRATE TO TUMORS experimental studies on the migration of MSCs are summarized in Table 1 and Table 2. These tables include several supporting clinical studies that have rigorously tracked the distribution of MSCs administered to patients. Taken together these studies demonstrate two important characteristics of MSCs: MSCs migrate toward tumors but this migration is non-specific [1 13 The migratory tropism toward tumors has been observed when MSCs are administered by intravenous  intraarterial  or peritumoral routes . The mechanism of migration is poorly understood but has Vitexin been shown to be dependent upon the cytokine/receptor pairs SDF-1/CXCR4 [15 17 18 SCF-c-Kit [19 20 HGF/c-Met  VEGF/VEGFR  PDGF/PDGFr  MCP-1/CCR2  and HMGB1/RAGE [24 25 as well as cellular adhesion molecules [18 26 27 Migration to tumors however is non-specific as exogenously administered MSCs have also been shown to localize to the lung [14 28 bone marrow [29 30 33 34 and lymphoid organs [35 36 and prior whole body irradiation tends to expand the distribution of MSCs in the body to multiple organs [28 30 Additionally MSCs appear to migrate to sites of localized chronic inflammation [35 37 which may in part explain the observation that MSCs are recruited in the process of wound repair [38-42]. Although MSCs have been shown to enhance metastatic potential in an animal model of breast carcinoma  there have been no reports of tumor seeding by MSCs in normal noncancerous tissue. These interactions between MSCs and normal noncancerous tissue however are probably very different from the relationships of MSCs with irregular Vitexin neoplastic cells. These relationships between MSCs and cancerous cells have been investigated more thoroughly and so are tackled in following parts of this review. Vitexin Desk 1 research of unmodified mesenchymal stem cell migration Desk 2 research of mesenchymal stem cells genetically revised by incorporation of the transgene IMMUNOSUPPRESSION BY MESENCHYMAL STEM CELLS Might FAVOR TUMOR Development In several pet tumor versions including melanoma [44 45 digestive tract adenocarcinoma  multiple myeloma  lung tumor  and glioblastoma  the current presence of exogenous MSCs was proven to enhance tumor development. Such studies offer indirect proof that.