Background Mesenchymal Progenitor/Stem Cells (MSC) respond to homing cues providing an

Background Mesenchymal Progenitor/Stem Cells (MSC) respond to homing cues providing an important mechanism to deliver therapeutics to sites of injury and tumors. MSCs in vivo and demonstrated an increased retention of MSC-AR in lungs expressing erbB2. We have also confirmed increased numbers of erbB2-targeted MSCs in ovarian tumors, compared to unmodified MSC. The kinetic of tumor targeting by ip injected MSC was also investigated. Conclusion These data demonstrate that targeting abilities of MSCs can be enhanced via introduction of artificial receptors. The application of this strategy for tumor cell-based delivery could increase a number of cell carriers in tumors and enhance efficacy of Cav1.2 cell-based therapy. Background In the last few years, cells have been increasingly used as vehicles for the delivery of therapeutics. The cell-based approach is particularly attractive for the delivery of biotherapeutic agents that are difficult to synthesize, have limited tissue penetrance, or are rapidly inactivated upon direct in vivo introduction. Some of Torin 2 the key factors for the success of this type of therapeutic delivery have been established, such as the means and efficiency of cell loading with a therapeutic payload, and the nature of therapeutics that the cells can carry. However, the issue of biodistribution of injected cell carriers in vivo still remains an important aspect of cell-based delivery that has yet to be fully investigated. Importantly, different types of cell vehicles may have specific biodistribution or cell homing patterns and, therefore, may provide a special advantage to achieve site-specific or targeted delivery of therapeutics. The ability of injected cells to either passively concentrate in specific organs or actively home to disease sites supports the rationale for targeted delivery of therapeutics by cell vehicles. There is growing Torin 2 evidence that sites of injury or growing tumors favor active homing of endogenous and exogenous stem or progenitor cells [1,2]. The first observation of this phenomenon was published by Studeny et al, using MSCs as vehicles delivering IFN [3]. This and a subsequent study by the same group [4] reported MSC localization in lung tumors after systemic injection of these cells. The recognition that the tumor microenvironment or tumor cytokine profile is similar to that of inflammatory sites evoked a search for the tumor attracting signals. Despite still incomplete knowledge of these cues, the practical aspects of cell-based delivery of therapeutics to specific sites have been actively exploited. A growing number of studies have used MSCs as cell vehicles to exploit their native ability to target tumors, as a means to track malignant tissues or for the delivery of anticancer Torin 2 agents to tumors [2,5-9]. Several studies investigated MSCs as cell vehicles for the delivery of various clinically relevant anticancer factors, including cytokines, interferons, pro-drugs and replication competent adenoviruses, with noted benefits [10-13]. The native tumor homing phenomenon of MSCs was confirmed in different experimental systems [2,12]. Other cell types, such as umbilical cord matrix stem cells (UCMS) [14], neural stem cells [15,16] and endothelial progenitor cells [17,18] have also demonstrated the inherent ability to migrate toward tumors or other pathologies. Along with using native cell homing properties, modification of the cell membrane by expressing appropriate receptors was also proposed as a means to obtain targeted cell vehicles. Much of the groundwork for such targeting approaches has previously been established for immune cells (T-cells, NK cells, CIK cells), where Torin 2 lymphocyte populations were modified to express artificial receptors (T-bodies) with distinct binding specificities to target cells. Artificial or chimeric receptors (AR) have been derived from the binding domains of antibodies (usually the single chain antibody, scFv) or T-cell receptors. An array of chimeric receptors, mostly with specificity for different tumor markers, has been tested for biological function in vitro [19,20] and in vivo [21,22]. This approach is often termed “targeted” adoptive immunotherapy, since the active targeting mechanism was added to redirect the native killing function of an immune cell to a defined target cell. Remarkably, the added affinity to retarget cell killing function was found to enhance localization.

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