24 Stem cells based delivery of therapeutics Different stem cell types have been genetically modified mainly to introduce and overexpress target exogenous genes for expression/secretion of a desired therapeutic factor for targeted treatment of different any other enquiries cancer types (Fig. 1).25 A number of studies have recently been published describing the successful use of stem cell based delivery of cytokines for the management of various human cancers. A few of the recent developments in this area are discussed below. Figure 1. Transgene strategies potentiating stem cells for tumor therapy. Tailored to the specific molecular profiles associated with individual tumor types, stem cells can be engineered with a variety of different anti-tumor agents (adapted …
Interleukins Stem cells have been efficiently employed for the delivery of interleukins in order to improve the anti-cancer immune surveillance by activating cytotoxic lymphocytes and natural killer cells. A number of previously published studies demonstrated the efficacy of stem cell delivered interleukin(IL)s such as IL-2,20 IL-7 [2], and IL-1826 in various tumors. However, MSC engineered to express interleukin (IL)-12 were recently shown to prevent metastasis into the lymph nodes and other internal organs as well as increased tumor cell apoptosis in mice bearing pre-established metastases of melanoma, breast and hepatoma tumors.27 Furthermore,, in a separate study, human umbilical cord blood�Cderived mesenchymal stem cells (UCB-MSCs) were successfully employed as delivery vehicles to deliver interleukin-12, a therapeutic gene in the management of malignant glioma.
28 In another study, human umbilical cord blood stem cells (UCBSCs) were engineered to express interleukin-21 (IL-21) and were shown to have therapeutic efficacy in mice bearing ovarian cancer xenografts. This study suggested that the UCBSC-IL-21 therapy was safe and feasible in ovarian cancer therapy, and that the method would be a promising new strategy for clinical treatment of ovarian cancer.29 Interferons Human bone marrow MSC secreting interferon (IFN) �C �� has been proven to have success in diminishing a number of tumors such as melanoma,30 breast cancer31 and lung metastases.32 In a recently published study, amniotic fluid derived mesenchymal stem cells (AF-MSCs) were isolated, investigated for their tumor tropism and capability to transport interferon-�� (IFN��) to the region of neoplasia in a bladder tumor model.
A significant inhibition of tumor growth as well as prolonged survival of mice was observed Cilengitide in the presence of AF-MSC-IFN��, thereby demonstrating the potential of engineered AF-MSCs as anti-cancer vehicles.33 In another study, adipose tissue derived stem cells were engineered to secrete IFN�� and were used in combination with the chemotherapeutic agent, cisplatin to demonstrate a marked reduction in tumor growth in a mouse model of melanoma.34 Yi et al.