The Singapore Research Centre: Developing Cellular Therapeutics

Cellular therapeutics is a growing field with tremendous potential. The possibilities range from the treatment of autoimmune, neurological, cardiovascular, and endocrinological diseases, to that of physical injuries and many other conditions in which cell repopulation or regeneration could alleviate if not totally cure the disorder.

Singapore's scientists and clinicians are enthusiastic about this emerging discipline and the therapeutic potential of stem cells in general. Earlier this week, doctors at the Singapore General Hospital (SGH) announced that they had performed the world's first successful pooled unrelated cord blood transplant using a nonmyeloablative (without removal of the bone marrow) approach. They effectively treated two blood cancer patients by using stem cell transplantation and without involving high-dose chemotherapy. SGH made news last July after using a similar procedure to treat a 5-year-old boy born with thalassemia major.

The nonmyeloablative stem cell transplant procedure adopted by the SGH team works on the basis that allergenic stem cells could engraft with a good immunosuppressive regimen. High-dose chemotherapy used conventionally to bring about myeloablation is therefore not required here. "The bone marrow, peripheral blood, and cord blood have been established as suitable sources of hematopoietic stem cells for transplantation," says Dr. William Hwang of the Department of Haematology at SGH. "Studies have shown that these may also be sources of totipotent cells, which can differentiate into other mesenchymal tissues. As such, the bone marrow and cord blood may provide suitable alternatives for the derivation of the stem cells we seek."

Asked about ethical concerns, Dr. Hwang replied, "Do we need to ravage the fetus for these cells when we may be able to develop techniques for isolating and growing stem cells from these other sources?" In fact, according to Hwang, "over 400 hematopoietic stem cell transplants have been performed at the Singapore General Hospital. We regularly perform such transplants on patients from Malaysia, Indonesia, Myanmar, Vietnam, India, and other countries. While standard approaches will still be performed, we are embarking on minimal-intensity regimens with novel sources (like the cord blood) for a wider spectrum of diseases (like the autoimmune diseases)," he added.

Over at the ES Cell International (ESI) research center at the National University of Singapore, Professor Ariff Bongso and his team are working toward large-scale production of pure populations of human embryonic stem (hES) cells for use in cell transplantation therapies. This work underpins the research programs at ESI's research centers worldwide, which focus on deriving specialized nerve, heart, and blood cells from hES cells, specifically for the treatment of neurological and cardiovascular degenerative diseases, and for blood diseases such as leukemias.

"Stem cell researchers in Singapore have shown significant interest in obtaining our hES cells, and we will continue to pursue opportunities for Singapore research collaborations," says ESI's chief operating officer, Catriona King. "With the establishment of other biotechnology companies with technologies that complement ESI's technology platform, Singapore is poised to become a major player in the world arena in the field of regenerative medicine."

The recent decision by ViaCell Singapore Pte Ltd (a wholly owned subsidiary of Boston-based ViaCell Inc.) to establish the Singapore Research Centre (SRC) * represents a bold new initiative to push Singapore toward the forefront of this emerging field of research. Dedicated to facilitating the development of cellular therapies here, SRC will explore areas such as stem cell biology, protein chemistry, stem cell markers, and growth factors in conjunction with ViaCell's patented Selective Amplification stem cell expansion technology. This proprietary technology, which has recently been cleared for clinical trials by the U.S. Food and Drug Administration, combines techniques for cell purification and cell culture that yield a significantly increased number of defined, pharmaceutical-grade stem cell populations from cells found in umbilical cord blood, bone marrow, and peripheral blood.

The groundbreaking venture--ViaCell's first international research facility--is expected to start operation next month under the directorship of Stephen Bartelmez, formerly of the University of Washington. According to ViaCell's chief executive officer, Mark Beer, SRC will enhance ViaCell's research efforts and support its mission to develop, manufacture, and market innovative cellular therapies for many unmet clinical challenges. With ViaCell's commitment, the future of developing cellular therapeutics here certainly appears promising. SRC's state-of-the-art facility is strategically located in the heart of the Singapore Science Hub and is expected to employ about 20 research scientists.

SRC is welcomed by many of Singapore's scientists. "We are encouraged by the government's commitment to bring in the best," says Alex Lee, a research scientist engaged in drug development. "This development recognizes Singapore's zeal to be in the forefront of stem cell research," acknowledges Valerie Lim, a postdoc who is optimistic about the future of cellular therapies. "ViaCell's scientific and technological expertise will pave the way for the development of novel therapeutics right here on Singapore's ground ... and that's exciting."

However, there are some who are concerned--with good reason--about the rapid development of cellular therapies in Singapore. With the worldwide storm of controversy over stem cell research nowhere near reaching a resolution, social and legal implications abound. Yet currently, there are no extensively applicable legal restrictions or commonly accepted ethical constraints on such research.

In Singapore, the Bioethics Advisory Committee is in the process of stipulating national guidelines for stem cell research. The Human Stem Cell Research Subcommittee, which was formed specifically to address the ethical, legal, and social issues associated with the use of human stem cells in biomedical research and development, drafted a consultation paper and distributed it to 38 organizations representing a wide variety of community groups for comments in November of last year. It has subsequently conducted dialogue sessions on the matter with various groups. The guidelines, due to be finalized and released shortly, will establish basic principles for Singapore's researchers and clinicians.

Obviously, stem cell researchers have a lot to go through before they will see the fruits of their research labor in routine medical applications. Here as elsewhere laboratory studies will have to be followed by clinical trials and subsequent follow-on studies, which will determine how applicable cellular therapeutics may be. But until the long-term viability of such therapies becomes clear, more efforts like those of the hematology group at SGH will be required to demonstrate the best that cellular therapeutics can offer.

* EDB is an investor in the Singapore Research Centre. EDB is the lead government agency that promotes and enhances the range of biomedical sciences activities in Singapore. EDB is also Next Wave Singapore's sponsor.

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