25 April 2012

Stem cells against cancer

IBN scientists are developing a promising alternative to traditional breast cancer treatments

Nanonewsnet based on the materials of the Institute of Bioengineering and Nanotechnology:
IBN Discovers Human Neural Stem Cells with Tumor Targeting Ability – A Promising Discovery for Breast Cancer TherapyCould engineered human stem cells be the key to cancer treatment?

Scientists from the Institute of Bioengineering and Nanotechnology (IBN), Singapore, the world's first research institute of bioengineering and nanotechnology, have discovered that neural stem cells have an innate ability to target tumor cells outside the central nervous system.

This discovery, successfully demonstrated on breast cancer cells, was recently published in the peer-reviewed scientific journal Stem Cells (Tumor Tropism of Intravenously Injected Human Induced Pluripotent Stem Cell-derived Neural Stem Cells and their Gene Therapy Application in a Metastatic Breast Cancer Model).

Despite decades of cancer research, this disease remains the leading cause of death worldwide, and breast cancer is one of its most dangerous forms. The high mortality rate from cancer is partly due to the ability of malignant tumors to invade – spread throughout the body – and the ineffectiveness of traditional therapies in the complete destruction of cancer cells.

A group of researchers led by Dr. Shu Wang (second from left in the picture) made a landmark discovery: neural stem cells (NSCs) derived from human induced pluripotent stem cells (iPS) can be used to treat breast cancer. The effectiveness of neural stem cells originating from cells of the central nervous system in the treatment of brain tumors has already been investigated. The work of scientists from IBN demonstrates for the first time that the targets of NSCs obtained from iPS can be both primary and secondary tumors outside the central nervous system.

To test the effectiveness of NSCs in targeting and treating breast cancer, scientists injected mice with breast tumors with NSCs loaded with the gene of the enzyme – thymidine kinase of the herpes simplex virus. Vectors obtained from baculovirus, an insect virus that does not replicate in human cells, which makes them less dangerous for clinical use, were chosen as carriers of this gene. Then the mice were injected with a non-toxic precursor drug (ganciclovir), which under the action of thymidine kinase turns into an active toxic agent.

The data obtained by visualization showed that the targets of iPS-NSCs were breast tumors. In addition, neural stem cells accumulated in various organs infiltrated by cancer cells – the lungs, stomach and bones. The survival period of mice with tumors increased from 34 to 39 days. These data confirm that engineered iPS-NSCs can effectively detect cancer cells and suppress tumor growth and spread.

"We have shown that tumor-oriented neural stem cells can be obtained from human iPS cells and that, in combination with a therapeutic gene, these cells can be used to suppress tumor growth," Dr. Wang comments on his work. "This is an important discovery for stem cell-based cancer therapy, and we will continue to refine and optimize our neural stem cell system to prevent any unwanted activation of the therapeutic gene in areas that do not contain tumor cells and minimize possible side effects."

Compared to obtaining and subsequent reproduction of the patient's own cells, the approach developed at IBN using induced pluripotent stem cells is less labor-intensive and suitable for large-scale production of unified batches of cellular products for repeated treatment of the patient. It is important to note that this approach will help eliminate differences in the quality of these products, thereby contributing to a reliable comparative analysis of clinical results.

In addition, NSCs are obtained from the cells of an adult organism, which makes it possible to circumvent the ethical problems associated with the use of human embryos, and since iPS cells are obtained from the patient's own cells, the probability of their immune rejection is significantly reduced.

"IBN's experience in obtaining human stem cells from iPS cells and our new use of insect virus carriers for gene delivery paved the way for the development of innovative stem cell-based therapy. A two–flank attack on tumors using genetically modified neural stem cells is a promising alternative to traditional cancer treatment," says IBN Executive Director Professor Jackie I. Yin (Jackie Y. Ying).

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