A research team at the University of Hong Kong's (HKU) Li Ka Shing Faculty of Medicine has become the first in the world successfully to generate human induced pluripotent stem cells (hiPSCs) without using animal products.

The announcement of the breakthrough was made Thursday by Professor Tse Hung-fat, William M W Mong professor in Cardiology and clinical professor at the Department of Medicine.

The importance of pluripotent stem cells is that they are able to form the basis for any fetal or adult cells. Scientists hope someday that stem cells will be capable of rebuilding damaged tissue in humans.

The latest development takes stem cell research a step closer to the clinical level by eliminating some of the risks entailed in the current approach to the generation of pluripotent cells, which uses human cells.

The standard protocol for generating hiPSCs requires animal cells and serum to feed the cells. This creates some risk that animal diseases and animal genetic materials might be transmitted during the generation process.

The HKU study, beginning in late 2008, found an alternative. The research team discovered a new protocol for a special enzyme inhibitor, which is widely used in the commercial market. After dozens of trials with different materials, the enzyme Rho kinase (ROCK) was shown to be the best substitute for animal cells for generating hiPSC, said Dr Siu, clinical assistant professor in the Department of Medicine and head of the research team.

The scientific team also experimented with transplantation of mesenchymal stem cells (MSC), which are hiPSC's generated from more mature human cells. MSCs have been shown, in mice experiments, to be capable of forming new blood vessels and improving circulation.

The research team was undertaking a study of critical limb ischemeia, a condition caused by poor blood circulation that often necessitates amputation of limbs among the elderly. The team was looking into potential clinical applications of stem cell therapy for the disease, which is common in Hong Kong and other developed countries, according to Professor Tse.

The study provides the first proof-of-concept evidence that hiPSC-based therapy can be used to treat human cardiovascular disease.

The hiPSC shares the same genetic composition as that of patients, and uncontrolled growth of the stem cells could lead to the development of tumors.

"By generating MSCs directly from hiPSCs, we can avoid the risk of tumor formation after transplantation. This is also a world-first," researcher Dr Lian Jianzhou, who is also assistant professor in the Department of Medicine and Eye Institute, told China Daily..

In addition to potential therapeutic application, hiPSC could be used as a tool to investigate various human diseases, professor Tse said. He and Dr Lian have been using the new hiPSC technology to study the origins of progeria, a dreadful disease that occurs once in every eight million live births, causing premature aging in children. Most of those afflicted die in their early teens.

In collaboration with the Stem Cell Consortium at A*STAR Institute of Medical Biology in Singapore, the team models the disease in the laboratory by generating hiPSCs from the skin of a progeria patient and turns them into various types of cells thus to study the disease process in different organs in a culture dish.

Despite the breakthroughs, Professor Tse said, it is still early to apply the hiPSC technology in the clinic.

"Currently we use viral agents to induce the cells in the hiPSC generation process, which is still a potential cause for tumors," he told reporters. "My conservative expectation would be in another two to three years at least (for the technology to be clinically applicable)."

The HKU team is now building up a disease specific-hiPSC library to model diseases that have no known cure.

China Daily

(HK Edition 01/14/2011 page1)