Abstract
Exploitation of the potential ability of human olfactory bulb (hOB) cells to carry, release, and deliver an effective, targeted anticancer therapy within the central nervous system (CNS) milieu remains elusive. Previous studies have demonstrated the marked ability of several types of stem cells (such as mesenchymal stem cells (MSCs) to carry and release different anti-cancer agents such as paclitaxel (PTX). Herein we investigate the ability of human olfactory bulb neural stem cells (Hu-OBNSCs) to carry and release paclitaxel, producing effective cytotoxic effects against cancer cells. We isolated Hu-OBNSCs from the hOB, uploaded them with PTX, and studied their potential cytotoxic effects against cancer cells in vitro. Interestingly, the Hu-OBNSCs displayed a five-fold increase in their resistance to the cytotoxicity of PTX, and the PTX-uploaded Hu-OBNSCs were able to inhibit proliferation and invasion, and to trigger marked cytotoxic effects on glioblastoma multiforme (GBM) cancer cells, and Human Caucasian fetal pancreatic adenocarcinoma 1 (CFPAC-1) in vitro. Despite their ability to resist the cytotoxic activity of PTX, the mechanism by which Hu-OBNSCs acquire resistance to PTX is not yet explained. Collectively our data indicate the ability of the Hu-OBNSCs to resist PTX, and to trigger effective cytotoxic effects against GBM cancer cells and CFPAC-1. This indicates their potential to be used as a carrier/vehicle for targeted anti-cancer therapy within the CNS.
Highlights
Targeting tumor cells and their associated microvessels by a drug that is toxic to them but of low toxicity to normal cells is the main goal of cancer chemotherapy
Hu-OBNSCs were grown in suspension aggregates as neurospheres and cultured in proliferation medium supplemented with the mitogens epidermal growth factor (EGF) and basic fibroblast growth factor (Figure 1A)
We demonstrated that Hu-OBNSCs can be uploaded with and can release PTX in a concentration that was able effectively to inhibit the proliferation of human glioblastoma cells (U87GM) and CFPAC-1 in vitro
Summary
Targeting tumor cells and their associated microvessels by a drug that is toxic to them but of low toxicity to normal cells is the main goal of cancer chemotherapy. Several approaches have been used to selectively transport such drugs into the tumor environment. Beside their potential application as an effective cellular therapy for central nervous system (CNS) degenerative and traumatic diseases, engineered neural stem cells (NSCs) might represent a new effective modality for cancer therapy [1]. The inherent ability of NSCs to hone into primary and metastatic tumor lesions within the nervous tissue might indicate their marked ability to serve as a promising delivery route for anti-cancer agents. The engrafted NSCs survived in the rat brain for more than eight weeks, and restored lost neuronal and glial cells [2,3,4]
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