– (ACN Newswire) – Could engineered human stem cells hold the key to cancer
survival? Scientists at the Institute
of Bioengineering and
Nanotechnology (IBN), the world’s first bioengineering and nanotechnology
research institute, have discovered that neural stem cells possess the innate
ability to target tumor cells outside the central nervous system. This finding,
which was demonstrated successfully on breast cancer cells, was recently
published in leading peer reviewed journal, Stem Cells.
Despite decades of cancer research, cancer remains a leading
cause of death worldwide, accounting for 7.6 million deaths in 2008, and breast
cancer is one of the most common causes of cancer deaths each year . In Singapore, more
than 1,400 women are diagnosed with breast cancer and more than 300 die as a
result of breast cancer each year . The high fatality rate of cancer is
partially attributed to the invasive ability of malignant tumors to spread
throughout the human body, and the ineffectiveness of conventional therapies to
eradicate the cancer cells.
A team of researchers led by IBN Group Leader, Dr Shu Wang,
has made a landmark discovery that neural stem cells (NSCs) derived from human
induced pluripotent stem (iPS) cells could be used to treat breast cancer. The
effectiveness of using NSCs, which originate from the central nervous system,
to treat brain tumors has been investigated in previous studies. This is the
first study that demonstrates that iPS cell-derived NSCs could also target
tumors outside the central nervous system, to treat both primary and secondary
To test the efficiency of NSCs in targeting and treating
breast cancer, the researchers injected NSCs loaded with a suicide gene (herpes
simplex virus thymidine) into mice bearing breast tumors. They did this using
baculoviral vectors or gene carriers engineered from an insect virus
(baculovirus), which does not replicate in human cells, making the carriers
less harmful for clinical use. A prodrug (ganciclovir), which would activate
the suicide gene to kill the cancerous cells upon contact, was subsequently
injected into the mice. A dual-colored whole body imaging technology was then
used to track the distribution and migration of the iPS-NSCs.
The imaging results revealed that the iPS-NSCs homed in on
the breast tumors in the mice, and also accumulated in various organs
infiltrated by the cancer cells such as the lung, stomach and bone. The
survival of the tumor-bearing mice was prolonged from 34 days to 39 days. This
data supports and explains how engineered iPS-NSCs are able to effectively seek
out and inhibit tumor growth and proliferation.
Dr Shu Wang shared, “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. 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.”
“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. With
their two-pronged attack on tumors using genetically engineered neural stem
cells, our researchers have discovered a promising alternative to conventional
cancer treatment,” added Professor Jackie. Y. Ying, IBN Executive
Compared to collecting and expanding primary cells from
individual patients, IBN’s approach of using iPS cells to derive NSCs is less
laborious and suitable for large-scale manufacture of uniform batches of
cellular products for repeated patient treatments. Importantly, this approach
will help eliminate variability in the quality of the cellular products, thus facilitating
reliable comparative analysis of clinical outcomes.
Additionally, these iPS cell-derived NSCs are derived from
adult cells, which bypass the sensitive ethical issue surrounding the use of
human embryos, and since iPS cells are developed from a patient’s own cells,
the likelihood of immune rejection would be reduced.
1. J. Yang, D. H. Lam, S. S. Goh, E. X. L. Lee, Y. Zhao, F. Chang Tay, C. Chen,
S. Du, G. Balasundaram, M. Shahbazi, C. K. Tham, W. H. Ng, H. C. Toh and S.
Wang, “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,” Stem Cells, (2012) DOI: 10.1002/stem.1051.
2. E. X. Lee, D. H. Lam, C. Wu, J. Yang, C. K. Tham and S.
Wang, “Glioma Gene Therapy Using Induced Pluripotent Stem Cell-Derived
Neural Stem Cells,” Molecular Pharmaceutics, 8 (2011) 1515-1524.
About the Institute
of Bioengineering and
The Institute of Bioengineering and Nanotechnology (IBN) was established in
2003 and is spearheaded by its Executive Director, Professor Jackie Yi-Ru Ying,
who has been on the Massachusetts Institute of Technology’s Chemical
Engineering faculty since 1992, and was among the youngest to be promoted to
Professor in 2001.
In 2008, Professor Ying was recognized as one of “One
Hundred Engineers of the Modern Era” by the American Institute of Chemical
Engineers for her groundbreaking work on nanostructured systems, nanoporous
materials and host matrices for quantum dots and wires.
Under her direction, IBN conducts research at the
cutting-edge of bioengineering and nanotechnology. Its programs are geared
towards linking multiple disciplines across engineering, science and medicine
to produce research breakthroughs that will improve healthcare and our quality
of life. For more information, please visit:www.ibn.a-star.edu.sg.
The Agency for Science, Technology and Research (A*STAR) is the lead agency for
fostering world-class scientific research and talent for a vibrant
knowledge-based and innovation-driven Singapore. A*STAR oversees 14
biomedical sciences and physical sciences and engineering research institutes,
and six consortia & centres, located in Biopolis and Fusionopolis as well
as their immediate vicinity. A*STAR supports Singapore’s key economic clusters
by providing intellectual, human and industrial capital to its partners in
industry. It also supports extramural research in the universities, and with
other local and international partners. For more information about A*STAR,