Potential breast cancer treatment: human neural stem cells can target tumors
Despite decades of cancer research, breast cancer remains a leading cause of illness and death worldwide. The second most common cancer in women next only to non-melanoma skin cancer, it’s responsible for about 13.7 percent of yearly cancer deaths of women worldwide and six percent of all yearly cancer deaths, in men and women combined.
And the numbers are rising — breast cancer has significantly increased since the 1970s. Modern lifestyles are largely responsible for the rise in breast cancer — its incidence is lowest in poor countries and highest in rich countries.
In women in the United States, about 230,480 new cases of invasive breast cancer were diagnosed in 2011, along with 57,650 new cases of non-invasive (in situ) breast cancer, and 2,140 new cases of invasive breast cancer in men. In the United Kingdom, breast cancer is the most common cancer there, with 48,034 new cases of breast cancer diagnosed in 2009 — over 99 percent of that in women.
Because of better treatments and more access to these, less women die from breast cancer today than they did 40 years ago, but the fatality rate is still relatively high — the rates vary from country to country, but overall, the rate is around 17 to 21 percent. This means that still one in five women who get breast cancer will die from the disease.
Why is this? Doctors say this is brought on by two reasons:
• Conventional therapies are still ineffective in getting rid of all cancer cells.
• Malignant tumors have the ability to spread throughout the human body.
Could engineered human stem cells hold the key to cancer survival?
Yes, and here’s how. Scientists from Singapore’s Institute of Bioengineering and Nanotechnology (IBN) recently made the landmark discovery that neural stem cells (NSCs) derived from human induced pluripotent stem (iPSCs) cells could be used to treat breast cancer. Their findings are published in the leading peer reviewed journal, Stem Cells.
The team, led by IBN Group Leader, Dr. Shu Wang, discovered that neural stem cells possess the innate ability to target tumor cells outside the central nervous system and then tested this successfully on breast cancer cells.
NSCs originate from the central nervous system, and have been demonstrated in previous studies to be effective in treating brain tumors. This is the first study to show that iPSC-derived NSCs can also target tumors outside the central nervous system — to treat both primary and secondary tumors.
Working with mice, the researchers set out to test the efficiency of NSCs in targeting and treating breast cancer. They started out by genetically engineering lab mice to develop breast tumors. They then injected these lab mice with NSCs loaded with a suicide gene — the herpes simplex virus thymidine.
The IBN investigators were careful to use gene carriers that are less harmful for use in lab experiments — baculoviral vectors. These are gene carriers engineered from an insect virus — the baculovirus — that can’t replicate in human cells.
Next, the researchers injected the mice with a prodrug — ganciclovir — that would activate the suicide gene to kill the cancerous cells upon contact.
Making use of a dual-colored whole body imaging technology to track the distribution and migration of the iPSCs-NSCs, the researchers found that:
• The iPSCs-NSCs also accumulated in various organs infiltrated by the cancer cells such as the lung, stomach and bone.
• But these iPSCs-NSCs also homed in on the breast tumors in the mice.
• The survival of the tumor-bearing mice was prolonged from 34 days to 39 days.
The IBN investigators conclude that iPSCs-NSCs are able to effectively seek out and inhibit tumor growth and proliferation.
What’s more, IBN’s approach of using iPSCs to derive NSCs is:
• Not laborious
• Suitable for large-scale manufacture of uniform batches of cellular products for repeated patient treatments
By contrast, for current stem cell treatments being developed, researchers typically collect and expand primary cells from individual patients. This is laborious and stem cells harvested can only be used on individual patients.
More importantly, the IBN approach will also help eliminate variability in the quality of the stem cell products — facilitating reliable comparative analysis of clinical outcomes.
• Since the iPSC-derived NSCs are derived from adult cells, the controversies over ethical issues surrounding the use of human embryos are avoided.
• Because iPSCs are developed from a patient’s own cells, the likelihood that they would be rejected by a body’s immune system is also drastically reduced.
“We have demonstrated that tumor-targeting neural stem cells may be derived from human iPS cells, and that these cells may be used in combination with a therapeutic gene to cripple tumor growth,” Dr. Shu Wang explains.
“This is a significant finding for stem cell-based cancer therapy, and we will continue to improve and optimize our neural stem cell system by preventing any unwanted activation of the therapeutic gene in non-tumor regions and minimizing possible side effects,” he adds.
“With their two-pronged attack on tumors using genetically engineered neural stem cells, our researchers have discovered a promising alternative to conventional cancer treatment,” says Professor Jackie. Y. Ying, IBN Executive Director.
“IBN’s expertise in generating human stem cells from iPS cells and our novel use of insect virus carriers for gene delivery have paved the way for the development of innovative stem cell-based therapies,” she says. Dr. Ying has been on the Massachusetts Institute of Technology’s Chemical Engineering faculty since 1992, and was promoted to full professor in 2001 — among the youngest to be promoted ever. In 2008, the American Institute of Chemical Engineers recognized her as one of “One Hundred Engineers of the Modern Era” by for her groundbreaking work on nanostructured systems, nanoporous materials and host matrices for quantum dots and wires.
Established in 2003, IBN is the world’s first bioengineering and nanotechnology research institute. It conducts cutting-edge bioengineering and nanotechnology research aimed to produce research breakthroughs that will improve healthcare and our quality of life.